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Mammary Gland (mammary + gland)
Kinds of Mammary Gland Terms modified by Mammary Gland Selected AbstractsORIGINAL ARTICLE: The Effect of High Gravidity on the Carcinogenesis of Mammary Gland in TA2 MiceAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010Xuan Wang Citation Wang X, Huang C, Sun B, Gu Y, Cui Y, Zhao X, Li Y, Zhang S. The effect of high gravidity on the carcinogenesis of mammary gland in TA2 mice. Am J Reprod Immunol 2010 Problem Spontaneous breast cancer in Tientsin Albinao 2 (TA2) mice, like human pregnancy-associated breast cancer (PABC), often occurs in pregnancy and puerperium, especially in mice with high gravidity. We hypothesized that the dysfunction of cellular immunity caused by the increase of 17,-estradiol (E2) and progesterone (P) might be one of the reasons for carcinogenesis of mammary gland. Method of study We investigated the T lymphocyte subsets and the concentration of serum hormone and cytokines in cancer-bearing, pregnant or postpartum TA2 mice using flow cytometry, chemiluminescent immunoassay, and enzyme-linked immunosorbent assay (ELISA), respectively. Results The number of T lymphocytes and the concentration of E2, P, interleukin-2 (IL-2), IL-4, and interferon-gamma (IFN-,) changed with the increase of pregnancy and puerperium. During four pregnancies, elevated E2 and P resulted in a decrease in the number of CD3+, CD4+ T lymphocytes, CD4+/CD8+ ratio, and the concentration of IL-2, IL-4, and IFN-,. Data in the fourth pregnancy were the closest to those of cancer-bearing mice. Conclusion T lymphocyte subsets and concentration of IL-2, IL-4, and IFN-, are affected by E2 and P during multiple pregnancy and delivery to some degree, which may contribute to the genesis of spontaneous breast cancer in TA2 mice. [source] Ultrastructural Morphometry of Mammary Gland in Transgenic and Non-transgenic RabbitsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2006S. Dragin Summary The mammary gland of transgenic animals has been used for the production of recombinant proteins of therapeutic and nutraceutical use. The objective of this study was to compare the ultrastructure of transgenic and non-transgenic rabbit mammary gland tissue. New Zealand White transgenic rabbits were obtained by breeding non-transgenic rabbits with transgenic founder rabbits containing a whey acidic protein-human factor VIII (WAP-hFVIII) transgene integrated into their genome. Samples of mammary gland tissue from lactating rabbit females were isolated by surgical procedures. These samples were examined by optical and electron microscopy and photographs were taken. Measurements of ultrastructural organelles were made from digital images of the mammary cells. No differences were found in the cellular structure of mammary tissue, but significant differences t(0.001) in the relative volume of mitochondria and vacuoles between transgenic and non-transgenic mammary gland epithelium were observed. [source] Adrenergic and Cholinergic Innervation of the Mammary Gland in the PigANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2002A. FRANKE-RADOWIECKA Adrenergic and acetylcholinesterase-positive (AChE-positive) innervation of the mammary gland in the sexually immature and mature pigs was studied using histochemical methods. Upon examining the adrenergic and cholinergic innervation, the adrenergic innervation was found to be much more developed. The majority of both sub-populations of the nerve fibres studied was localized in the subcutaneous tissue of the mammary gland. Adrenergic and AChE-positive nerve fibres also supplied structures of the nipple (subcutaneous tissue, blood vessels, smooth muscles fibres) and glandular tissue (blood vessels, lactiferous ducts). The glandular tissue contained the smallest number of adrenergic and AChE-positive nerve fibres. No distinct differences were observed in the adrenergic and AChE-positive innervation of the porcine mammary gland between the juvenile and non-pregnant adult animals. [source] Histological Features in the Mammary Glands of Female Dogs throughout LactationANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010D. C. Orfanou With 3 tables and 2 figures Summary The objective of this study was to describe the histology of the mammary glands of female dogs throughout lactation. Twelve lactating female dogs were operated 4, 7, 10, 14, 21, 28, 35, 42, 56, 70 and 84 days post-partum; four mammary glands of each animal were excised for histological, ultrastructural and morphometric examination. During early lactation and mid-lactation, all lobes and lobules within the same gland had similar features; alveoli were well developed and distended and had a spherical to slightly ovoid structure, with muscular fibres grasping them around; inflammatory cells were seen in the inter- and intra-alveolar space; mammary lobules were separated with a scant amount of connective tissue. In late lactation, connective tissue was abundant and dense, with large numbers of inflammatory cells; alveoli appeared to be irregularly shaped and collapsing, shrunken or fully collapsed. Number of alveoli per lobule and number of epithelial cells per alveolus, as well as diameter of alveoli and height of epithelial cells decreased as lactation progressed. The third mammary glands (from caudal to cranial) had a significantly smaller number of alveoli, but not of epithelial cells per alveolus, than each of the two mammary glands caudally to that. The results suggest that progressive involution of the normal mammary gland starts around the end of the 2nd month of lactation and continues until the end of the 3rd month. [source] The Lymph Drainage Pattern of the Mammary Glands in the Cat: A Lymphographic and Computerized Tomography Lymphographic StudyANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2009P. L. Papadopoulou Summary Seventy-three clinically normal, lactating cats were used to investigate the lymph drainage of 73 mammary glands. In 50 cats of the first group, the number of lymphatic vessels emerging from the examined mammary gland, their course and the lymph nodes into which they are drained were studied by indirect lymphography (IL) after intramammary injection of an oily contrast medium. In 23 cats of the second group, the lymph drainage of the mammary glands was studied by computerized tomography indirect lymphography (CT-IL) after intramammary injection of a water soluble contrast medium. The following day, the lymph drainage of the mammary gland examined by CT-IL was studied by IL, as it was described in the first group, for comparison purposes. The main conclusions drawn after this study were as follows: lymph drains from the first and second mammary glands with one or rarely two or three lymphatic vessels to the accessory axillary lymph nodes. Lymph drains from the third mammary gland with one or two and rarely three lymphatic vessels usually to the accessory inguinal lymph nodes or to the accessory axillary lymph nodes. In some cases, it drains to both lymph nodes simultaneously or it may rarely drain only to the medial iliac lymph nodes. The fourth mammary gland with one or two and rarely three lymphatic vessels usually drains to the accessory inguinal lymph nodes. It may rarely drain only to the medial iliac lymph nodes. Mammary lymphatic vessels that cross the midline and lymphatic connection between the mammary glands were not demonstrated. No differences in the mammary lymph drainage pattern between IL and CT-IL were found. [source] Effect of N-cadherin misexpression by the mammary epithelium in miceJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2005Karen A. Knudsen Abstract N-cadherin is not typically expressed by epithelial cells. However, it is detected in breast cancers and increases tumor cell migration and invasion in vitro. To explore its misexpression, we generated transgenic mice with N-cadherin in the mammary epithelium. Mammary glands appeared normal and no tumors arose spontaneously. To investigate N-cadherin misexpression in mammary tumors, neu was overexpressed through breeding. Tumors developed in +/neu and N-cadherin/neu mice, although few tumors in bitransgenic mice expressed N-cadherin, and they did not differ from N-cadherin-negative tumors. © 2005 Wiley-Liss, Inc. [source] Sdmg1 is a component of secretory granules in mouse secretory exocrine tissuesDEVELOPMENTAL DYNAMICS, Issue 1 2009Diana Best Abstract Sdmg1 is a conserved eukaryotic transmembrane protein that is mainly expressed in the gonads where it may have a role in mediating signaling between somatic cells and germ cells. In this study we demonstrate that secretory exocrine cells in the pancreas, salivary gland, and mammary gland also express Sdmg1. Furthermore, we show that Sdmg1 expression is up-regulated during pancreas development when regulated secretory granules start to appear, and that Sdmg1 colocalizes with secretory granule markers in adult pancreatic acinar cells. In addition, we show that Sdmg1 co-purifies with secretory granules during subcellular fractionation of the pancreas and that Sdmg1 and the secretory granule marker Vamp2 are localized to distinct subdomains in the secretory granule membrane. These data suggest that Sdmg1 is a component of regulated secretory granules in exocrine secretory cells and that the developmental regulation of Sdmg1 expression is related to a role for Sdmg1 in post-Golgi membrane trafficking. Developmental Dynamics 238:223,231, 2009. © 2008 Wiley-Liss, Inc. [source] Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary glandDEVELOPMENTAL DYNAMICS, Issue 1 2006Richard P. Metz Abstract Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation, and differentiation marker genes. Expression of the clock genes Per1 and Bmal1 were elevated in differentiated HC-11 cells, whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands, as Per1 and Bmal1 mRNA levels were elevated in late pregnant and lactating mammary tissues, whereas Per2 expression was higher in proliferating virgin and early pregnant glands. In both HC-11 cells and mammary glands, elevated Per2 expression was positively correlated with c-Myc and Cyclin D1 mRNA levels, whereas Per1 and Bmal1 expression changed in conjunction with ,- casein mRNA levels. Interestingly, developmental stage had differential effects on rhythms of clock gene expression in the mammary gland. These data suggest that circadian clock genes may play a role in mouse mammary gland development and differentiation. Developmental Dynamics 235:263,271, 2006. © 2005 Wiley-Liss, Inc. [source] Retinoic acid signaling is required for proper morphogenesis of mammary glandDEVELOPMENTAL DYNAMICS, Issue 4 2005Y. Alan Wang Abstract Retinoic acid (RA), a bioactive chemical compound synthesized from dietary derived vitamin A, has been successfully used as a chemopreventive and chemotherapeutic agent through the regulation of cell proliferation, differentiation, and apoptosis acting via the retinoic acid receptors. Despite two decades of research on the function of retinoic acid, the physiological role of RA in mammary gland development is still not well characterized. In this report, we demonstrate that RA is required for proper morphogenesis of mouse mammary gland in a novel transgenic mouse model system. It was found that inhibition of RA signaling in vivo leads to excessive mammary ductal morphogenesis through upregulation of cyclin D1 and MMP-3 expression. Furthermore, we show that the transgene-induced excessive branching morphogenesis could be reversed by treatment with RA, demonstrating the direct physiological effect of RA signaling in vivo. In addition, we demonstrate that excessive branching morphogenesis in the transgenic mammary gland are cell-autonomous and do not require stromal signals within the transgenic mammary gland. Finally, we provide evidence suggesting that retinoic acid signaling is required for appropriate mammary gland differentiation. Collectively, our data indicate for the first time that retinoic acid signaling is required to maintain the homeostasis of mammary gland morphogenesis. Developmental Dynamics 234:892,899, 2005. © 2005 Wiley-Liss, Inc. [source] Adipocyte prolactin: regulation of release and putative functionsDIABETES OBESITY & METABOLISM, Issue 4 2007T. Brandebourg Pituitary-derived prolactin (PRL) is a well-known regulator of the lactating mammary gland. However, the recent discovery that human adipose tissue produces PRL as well as expresses the PRL receptor (PRLR) highlights a previously unappreciated action of PRL as a cytokine involved in adipose tissue function. Biologically active PRL is secreted by all adipose tissue depots examined: breast, visceral and subcutaneous. The expression of adipose PRL is regulated by a non-pituitary, alternative superdistal promoter. PRL expression and release increases during early pre-adipocyte differentiation and is stimulated by cyclic AMP activators, including , adrenergic receptor agonists. PRL release from subcutaneous adipose explants is attenuated during obesity, suggesting that adipose PRL production is altered by the metabolic state. Several lines of evidence indicate that PRL suppresses lipid storage as well as the release of adipokines such as adiponectin, interleukin-6 and possibly leptin. PRL has also been implicated in the regulation of adipogenesis. A newly developed PRL-secreting human adipocyte cell line, LS14, should allow comprehensive examination of the regulation and function of adipocyte-derived PRL. Collectively, these studies raise the prospect that PRL affects energy homeostasis through its action as an adipokine and is involved in the manifestation of insulin resistance. [source] Environmental carcinogens and p53 tumor-suppressor gene interactions in a transgenic mouse model for mammary carcinogenesisENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002Daniel Medina Abstract Mouse mammary tumorigenesis is greatly influenced by a variety of exogenous agents, such as MMTV, chemical carcinogens (i.e., polycyclic aromatic hydrocarbons), and radiation, as well as by endogenous/physiological factors, such as steroid hormones, tumor-suppressor genes (i.e., Brca1/2,p53), and gene products of modifier genes. In the mouse model, the most frequently used chemical carcinogen has been 7,12-dimethylbenz[a]anthracene (DMBA), which activates the Ha- ras gene but does not alter the p53 tumor-suppressor gene. However, on an existing background of p53 gene alteration, low doses of DMBA are strongly cocarcinogenic. Using a transgenic model system, in which the p53 gene was deleted in the mammary gland, we examined the carcinogenic effects of a variety of external agents and internal factors given at either low doses or physiological doses. These agents/factors included DMBA, ,-radiation, Brca2 heterozygosity, and steroid hormones. All agents/factors increased the tumorigenic response of the p53 null mammary cells, even under conditions where no tumorigenic response was observed in the p53 wildtype mammary cell. The strongest cocarcinogenic effect was observed with the steroid hormone progesterone. The majority of tumors were highly aneuploid and composed of nuclear igh-grade cells. The mechanism for the aneuploidy and secondary events associated with high tumorigenicity were examined using array technology. These results demonstrate that, on a background of underlying genetic instability, very low doses of environmental mutagens and mitogens can produce strong cocarcinogenic effects. Environ. Mol. Mutagen. 39:178,183, 2002. © 2002 Wiley-Liss, Inc. [source] 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP),induced mutagenesis in cultured Big BlueÔ rat mammary epithelial and fibroblast cellsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002Heather M. McDiarmid Abstract Epithelial cells are the primary site of carcinogenesis in most tissues, including the mammary gland. As an alternative to the study of mutation induction in whole tissues in vivo, we have established Big BlueÔ transgenic rat cell lines from the mammary epithelium (BBR/ME) and the mammary stroma (BBR/MFib), to permit a comparison of their mutagenic responses to carcinogens. We previously demonstrated their responsiveness to the alkylating agent N -ethyl- N -nitrosourea (ENU) (McDiarmid H et al. [2001]: Mutat Res 497:39,47). Here, we examined the responses of cultured epithelial and stromal cells to the protein pyrolysis product and mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Rat hepatic S9 was used as a source of bioactivation enzymes. Mutant induction (cII locus) and clonogenic survival were measured as a function of PhIP concentration. PhIP mutagenicity was observed in the fibroblast cells, but the greater toxicity of PhIP to the epithelial cells prevented a definitive evaluation of mutagenicity. Since PhIP may be detoxified by conjugation with glutathione, we measured glutathione levels and glutathione- S -transferase expression and activities in both cell lines. The epithelial cells had higher glutathione- S -transferase enzyme activity and protein expression than did the fibroblast cell line. Because the epithelial cells were more sensitive to toxicity, glutathione conjugation evidently plays only a minor role in PhIP toxicity and mutagenicity in our cell lines. Environ. Mol. Mutagen. 39:245,253, 2002. © 2002 Wiley-Liss, Inc. [source] Tissue-specific distribution and whole-body burden estimates of persistent organic pollutants in the bottlenose dolphin (Tursiops truncatus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010Jennifer E. Yordy Abstract Most exposure assessments for free-ranging cetaceans focus on contaminant concentrations measured in blubber, and few data are available for other tissues or the factors governing contaminant distribution among tissues. The goal of this study was to provide a detailed description of the distribution of persistent organic pollutants (POPs) within the common bottlenose dolphin (Tursiops truncatus) body and assess the role of lipid dynamics in mediating contaminant distribution. Thirteen tissues (brain, blubber, heart, liver, lung, kidney, mammary gland, melon, skeletal muscle, spleen, thyroid, thymus, and testis/uterus) were sampled during necropsy from bottlenose dolphins (n,=,4) and analyzed for lipid and 85 POPs, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers. Significant correlations between tissue POP concentrations and lipid suggest that distribution of POPs is generally related to tissue lipid content. However, blubber:tissue partition coefficients ranged widely from 0.753 to 6.25, suggesting that contaminant distribution is not entirely lipid-dependent. Tissue-specific and whole-body contaminant burdens confirmed that blubber, the primary site of metabolic lipid storage, is also the primary site for POP accumulation, contributing >90% to the whole-body burdens. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue concentrations. These results suggest that individuals with reduced blubber lipid may be at increased risk for exposure-related health effects. However, this study also provides evidence that the melon, a metabolically inert lipid-rich structure, may serve as an alternate depot for POPs, thus preventing the bulk of blubber contaminants from being directly available to other tissues. This unique physiological adaptation should be taken into consideration when assessing contaminant-related health effects in wild cetacean populations. Environ. Toxicol. Chem. 2010;29:1263,1273. © 2010 SETAC [source] Differential diagnosis and treatment of diseases of the equine mammary glandEQUINE VETERINARY EDUCATION, Issue S5 2002A. J. McGladdery No abstract is available for this article. [source] Expression of the whey acidic protein (Wap) is necessary for adequate nourishment of the offspring but not functional differentiation of mammary epithelial cellsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 1 2005Aleata A. Triplett Abstract Whey acidic protein (WAP) is the principal whey protein found in rodent milk, which contains a cysteine-rich motif identified in some protease inhibitors and proteins involved in tissue modeling. The expression of the Wap gene, which is principally restricted to the mammary gland, increases more than 1,000-fold around mid-pregnancy. To determine whether the expression of this major milk protein gene is a prerequisite for functional differentiation of mammary epithelial cells, we generated conventional knockout mice lacking two alleles of the Wap gene. Wap-deficient females gave birth to normal litter sizes and, initially, produced enough milk to sustain the offspring. The histological analysis of postpartum mammary glands from knockout dams does not reveal striking phenotypic abnormalities. This suggests that the expression of the Wap gene is not required for alveolar specification and functional differentiation. In addition, we found that Wap is dispensable as a protease inhibitor to maintain the stability of secretory proteins in the milk. Nevertheless, a significant number of litters thrived poorly on Wap-deficient dams, in particular during the second half of lactation. This observation suggests that Wap may be essential for the adequate nourishment of the growing young, which triple in size within the first 10 days of lactation. Important implications of these findings for the use of Wap as a marker for advanced differentiation of mammary epithelial cells and the biology of pluripotent progenitors are discussed in the final section. genesis 43:1,11, 2005. © 2005 Wiley-Liss, Inc. [source] Cre-mediated recombination in cell lineages that express the progesterone receptorGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2005Selma M. Soyal Abstract Using gene-targeting methods, a progesterone receptor Cre knockin (PR-Cre) mouse was generated in which Cre recombinase was inserted into exon 1 of the PR gene. The insertion positions the Cre gene downstream (and under the specific control) of the endogenous PR promoter. As for heterozygotes for the progesterone receptor knockout (PRKO) mutation, mice heterozygous for the Cre knockin insertion are phenotypically indistinguishable from wildtype. Crossing the PR-Cre with the ROSA26R reporter revealed that Cre excision activity is restricted to cells that express PR in progesterone-responsive tissues such as the uterus, ovary, oviduct, pituitary gland, and mammary gland. Initial characterization of the PR-Cre mouse underscores the utility of this model to precisely ablate floxed target genes specifically in cell lineages that express the PR. In the wider context of female reproductive tissue ontology, this model will be indispensable in tracing the developmental fate of cell lineages that descend from PR positive progenitors. genesis 41:58,66, 2005. © 2005 Wiley-Liss, Inc. [source] Redistribution of the sheep neonatal Fc receptor in the mammary gland around the time of parturition in ewes and its localization in the small intestine of neonatal lambsIMMUNOLOGY, Issue 3 2002Balázs Mayer Summary Maternal immunity is mediated exclusively by colostral immunoglobulins in ruminants. As the neonatal Fc receptor (FcRn) is suggested to be involved in the transport of immunoglobulin G (IgG) in the mammary gland, we cloned this receptor from sheep and analysed its expression in the mammary gland around the time of parturition and also in the small intestine from the newborn lamb. FcRn heavy-chain mRNA was detected (by using in situ hybridization) exclusively in the acinar and ductal epithelial cells in mammary gland biopsies both before and after parturition. Immunohistochemistry revealed that the cytoplasm of the epithelial cells of the acini and ducts in the mammary gland biopsies stained homogeneously before parturition. A remarkable difference was observed in the pattern after lambing, where the apical side of the cells was strongly stained. The presence of the FcRn in the acinar and ductal epithelial cells of the mammary gland, and the obvious change in distribution before and after parturition, indicate that the FcRn plays an important role in the transport of IgG during colostrum formation in ruminants. Immunohistochemical analysis detected a strong apical and a weak basal FcRn signal in the duodenal crypt cells of a neonatal lamb, which have been previously demonstrated to secrete IgG1 in newborn ruminants. The FcRn was not detected in the duodenal enterocytes, which absorb intact IgG from the colostrum in a non-specific manner. These data suggest that FcRn is involved in IgG1 secretion in ruminant epithelial cells. [source] The 8-epimer of prostaglandin F2,, a marker of lipid peroxidation and oxidative stress, is decreased in the nipple aspirate fluid of women with breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Ferdinando Mannello Abstract Breast cancer (BC), a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess breast metabolic activity. Whether lipid peroxidation in the mammary gland promotes or prevents tumorigenesis is unclear. Malondialdehyde (MDA) and the 8-epimer of Prostaglandin F2, (8-iso-PGF2,), two lipid peroxidation markers, were studied in milk (n = 10), NAF (n = 140) and plasma (n = 35) samples. MDA was detected in all plasma, in 80% of milk samples and in 95% of NAF samples. MDA levels in NAF and plasma were significantly higher than in milk (p = 0.016 and p = 0.029, respectively). We found no significant difference between levels of MDA in NAF samples from BC patients compared to healthy controls. 8-iso-PGF2, was detectable in all samples. 8-iso-PGF2, median levels in NAF were significantly higher than in both milk and plasma (p < 0.0001). The highest 8-iso-PGF2, levels were found in NAF from healthy women, significantly higher than in women with BC (p < 0.0001). No significant differences were found in both markers after the age-adjustment. High levels of lipid peroxidation products in NAF suggest their in situ production in the nonlactating breast. Active lipid peroxidation may have a physiologic role in the normal mammary gland. Lower levels of 8-iso-PGF2, in NAF from BC patients suggest altered production of arachidonic acid metabolites during breast carcinogenesis. © 2006 Wiley-Liss, Inc. [source] Deregulation of Stat5 expression and activation causes mammary tumors in transgenic miceINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Elena Iavnilovitch Abstract Members of the signal transducers and activators of transcription (Stat) family regulate essential cellular growth and survival functions in normal cells and have also been implicated in tumorigenesis. We have studied the potential role of Stat5 in mammary tumorigenesis by targeting Stat5 variants to the mammary gland of transgenic mice using regulatory sequences of the ,-lactoglobulin gene. Mammary-directed expression of the wild-type Stat5, constitutively activated Stat5 and carboxyl-terminally truncated dominant negative Stat5 forms resulted in mammary tumors with incidence rates of up to 22% and latency periods of 8,12 months. Undifferentiated carcinomas most frequently occurred in mice expressing the carboxyl-terminally truncated Stat5. The more differentiated papillary and micropapillary adenocarcinomas were primarily found in mice overexpressing the native and constitutively active transgenes. Higher levels of translation initiation factor 4E (eIF4E) and cyclin D1 expression but lower levels of activated Stat3 were found in tumors of mice expressing the constitutively active Stat5 when compared to mice expressing the wild-type or truncated forms. A higher expression of the estrogen receptor (ER,) was observed in carcinomas compared to other phenotypes. The ability of both forms of Stat5, the transactivating form and the dominant negative form, to participate in oncogenesis indicates that there is more than one mechanism by which Stat5 contributes to this process. The transactivation function of Stat5 is involved in the determination of tumors with a more differentiated phenotype. © 2004 Wiley-Liss, Inc. [source] BRIEF COMMUNICATION: Histology of the pouch epithelium and the mammary glands during chemically induced oestrus in the brushtail possum (Trichosurus vulpecula)JOURNAL OF ANATOMY, Issue 1 2005Julie M. Old Abstract Changes in the epithelium of the maternal pouch and the mammary gland of brushtail possums (Trichosurus vulpecula) were examined after animals were treated to induce ovulation with follicle-stimulating hormone (FSH), luteinizing hormone (LH), pregnant mares' serum gonadotrophin (PMSG) and oestradiol. The mammary glands were similar in appearance to those described in eutherian mammals and in previous studies on other marsupials. Exposure of possums to these compounds, particularly PSMG, appeared to result in changes in the mammary glands that could be associated with milk/secretion production. In contrast, the pouch epithelium had a similar histological appearance to that of epithelium from other parts of the body regardless of whether the animal was exposed to stimulants. These preliminary observations are discussed in the context of the purported role of the pouch epithelium and the mammary gland in production of secretions at oestrus and provision of immunological protection to the neonatal marsupial. [source] Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryosJOURNAL OF ANATOMY, Issue 1 2004Maxwell C. Eblaghie Abstract Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and the same gene families have been implicated in mammary gland development. Here we explore how these genes act together in mammary gland initiation. We compared expression of Tbx3, the gene associated with the human condition ulnar,mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a transcription factor mediating Wnt signalling and the earliest gene so far known to be expressed in mammary gland development. We found that Tbx3 is expressed earlier than Lef1 and that Pyst1 is also expressed early but only transiently. Patterns of expression of Tbx3, Pyst1 and Lef1 in different glands suggest that the order of mammary gland initiation is 3, 4, 1, 2 and 5. Consistent with expression of Pyst1 in the mammary gland, we detected expression of Fgfr1b, Fgf8 and Fgf9 in both surface ectoderm and mammary bud epithelium, and Fgf4 and Fgf17 in mammary bud epithelium. Beads soaked in FGF-8 applied to the flank of mouse embryos, at a stage just prior to mammary bud initiation, induce expression of Pyst1 and Lef1 and maintain Tbx3 expression in flank tissue surrounding the bead. Grafting beads soaked in the FGFR1 inhibitor, SU5402, abolishes Tbx3, Pyst1 and Lef1 expression, supporting the idea that FGFR1 signalling is required for early mammary gland initiation. We also showed that blocking Wnt signalling abolishes Tbx3 expression but not Pyst1 expression. These data, taken together with previous findings, suggest a model in which Tbx3 expression is induced and maintained in early gland initiation by both Wnt and Fgf signalling through FGFR1. [source] Phagocytic capacity of leucocytes in sheep mammary secretions following weaningJOURNAL OF ANATOMY, Issue 5 2002Liliana Tatarczuch Abstract Lactating animals are particularly susceptible to mastitis during the early stages of mammary gland involution following weaning. In this study we compared the phagocytic capacity of cells collected from sheep mammary secretions at different stages of involution. The ability of neutrophils and macrophages to ingest latex beads in an in vitro phagocytosis assay was found to be dependent on how heavily the phagocytes were loaded with milk constituents. There was a decline in the phagocytic capacity of neutrophils from 1 to 2 days after weaning, while macrophages collected from fully involuted glands were more effective phagocytes compared with earlier stages (7,15 days) of involution. In addition, dendritic cells present in fully involuted mammary gland secretions (30 days after weaning) were highly phagocytic. These studies demonstrate that neutrophils and macrophages in sheep mammary secretions at early stages of involution are incapacitated, and as such may compromise the immune status of the mammary gland. [source] TELOCYTES , a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTESJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2010L. M. Popescu Abstract Ramon y Cajal discovered a particular cell type in the gut, which he named ,interstitial neurons' more that 100 years ago. In the early 1970s, electron microscopy/electron microscope (EM) studies showed that indeed a special interstitial cell type corresponding to the cells discovered by Cajal is localized in the gut muscle coat, but it became obvious that they were not neurons. Consequently, they were renamed ,interstitial cells of Cajal' (ICC) and considered to be pace-makers for gut motility. For the past 10 years many groups were interested in whether or not ICC are present outside the gastrointestinal tract, and indeed, peculiar interstitial cells were found in: upper and lower urinary tracts, blood vessels, pancreas, male and female reproductive tracts, mammary gland, placenta, and, recently, in the heart as well as in the gut. Such cells, now mostly known as interstitial Cajal-like cells (ICLC), were given different and confusing names. Moreover, ICLC are only apparently similar to canonical ICC. In fact, EM and cell cultures revealed very particular features of ICLC, which unequivocally distinguishes them from ICC and all other interstitial cells: the presence of 2,5 cell body prolongations that are very thin (less than 0.2 ,m, under resolving power of light microscopy), extremely long (tens to hundreds of ,m), with a moniliform aspect (many dilations along), as well as caveolae. Given the unique dimensions of these prolongations (very long and very thin) and to avoid further confusion with other interstitial cell types (e.g. fibroblast, fibrocyte, fibroblast-like cells, mesenchymal cells), we are proposing the term TELOCYTES for them, and TELOPODES for their prolongations, by using the Greek affix ,telos'. [source] Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2005Transmission electron microscope (TEM) identification Abstract We have previously shown the existence of ICLC in human resting mammary gland stroma by means of methylene blue (vital) staining and c-kit immunopositivity (immunofluorescence and immunohistochemistry). In addition, we reported the phenotype characteristics of these ICLC in vitro (primary cell cultures). Since the identification of ICLC outside the gut requires, at this moment, the obligatory use of TEM, we used this technique and provide unequivocal evidence for the presence of ICLC in the intralobular stroma of human resting mammary gland. According to the,platinum standard' (10 TEM criteria for the certitude diagnosis of ICLC), we found interstitial cells with the following characteristics: 1. location: among the tubulo-alveolar structures, in the non-epithelial space; 2. caveolae:,2.5% of cell volume; 3. mitochondria:,10% of cell volume; 4. endoplasmic reticulum: either smooth or rough, ,2,3% of cell volume; 5. cytoskeleton: intermediate and thin filaments, as well as microtubules are present; 6.myosin thick filaments: undetectable; 7. basal lamina: occasionally found; 8. gap junctions: occasionally found; 9. close contacts with targets: nerve fibers, capillaries, immunoreactive cells by ,stromal synapses'; 10. characteristic cytoplasmic processes: i) number: frequently 2,3; ii) lenght: several tens of ,m; iii) thickness: uneven caliber, 0.1,0.5 ,m, with dilations, but very thin from the emerging point; iv) aspect: moniliform, usually with mitochondria located in dilations; y) branching: dichotomous pattern; vi) Ca2+ release units: are present; vii) network labyrinthic system: overlapping cytoplasmic processes. It remains to be established which of the possible roles that we previously suggested for ICLC (e.g. juxta- and/or paracrine secretion, uncommited progenitor cells, immunological surveillance, intercellular signaling, etc.) are essential for the epithelium/stroma equilibrium in the mammary gland under normal or pathological conditions. [source] P-cadherin expression in canine lactating mammary glandJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2002Adelina Gama No abstract is available for this article. [source] TGF-, induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathwaysJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2008Charlotte Tacheau One of the shared physiological roles between TGF-, and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-,1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-,1 plays a key role in the control of NMuMG cells proliferation by TGF-,1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-,1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-,1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-,1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-,1-induced Cx43 gene expression. J. Cell. Physiol. 217: 759,768, 2008. © 2008 Wiley-Liss, Inc. [source] STAT proteins: From normal control of cellular events to tumorigenesis,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2003Valentina Calň Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFN, signaling. The other group includes STAT1, STAT3, and STAT5, activated in different tissues by means of a series of ligands and involved in IFN signaling, development of the mammary gland, response to GH, and embriogenesis. This latter group of STATS plays an important role in controlling cell-cycle progression and apoptosis and thus contributes to oncogenesis. Although an increased expression of STAT1 has been observed in many human neoplasias, this molecule can be considered a potential tumor suppressor, since it plays an important role in growth arrest and in promoting apoptosis. On the other hand, STAT3 and 5 are considered as oncogenes, since they bring about the activation of cyclin D1, c-Myc, and bcl-xl expression, and are involved in promoting cell-cycle progression, cellular transformation, and in preventing apoptosis. J. Cell. Physiol. 197: 157,168, 2003© 2003 Wiley-Liss, Inc. [source] TNF, induces NF,B/p50 in association with the growth and morphogenesis of normal and transformed rat mammary epithelial cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2001Linda M. Varela In contrast to the cytotoxic or cytostatic effect of TNF, on many breast cancer cell lines, TNF, stimulates growth and morphogenesis of normal rat mammary epithelial cells (MEC). The present studies were carried out to determine whether there are intrinsic differences between normal and malignant MEC which may explain the differing responsiveness to TNF,. Freshly isolated rat MEC organoids from normal mammary gland or 1-methyl-1-nitrosourea-induced mammary tumors were treated with TNF, for 21 days. Unexpectedly, TNF, stimulated growth and morphogenesis of both normal and transformed MEC in primary culture, although in transformed cells its effects were delayed and the majority of the colonies were histologically abnormal, with multiple cell layers and no lumen. Since NF,B is a key mediator of TNF, action and has been implicated in carcinogenesis, the expression of the p50, p52, p65, and c-rel NF,B proteins in normal and transformed MEC was determined. Expression of p52 was significantly reduced in tumor cells, and p50 was absent, although its putative precursor, p105 was abundant. There were no changes in the levels of p65 or c-rel. TNF, induced a pronounced and sustained increase of a p50 homodimeric NF,B/DNA complex in both normal and transformed MEC. However, in transformed MEC, NF,B binding was initially undetectable but then increased in response to TNF,. Thus, NF,B expression and DNA binding activity are altered during mammary carcinogenesis. In addition, the significant increase in NF,B/p50 DNA-binding was temporally coincident with TNF,-induced growth and morphogenesis, suggesting that it may play a significant role in both normal development and carcinogenesis. © 2001 Wiley-Liss, Inc. [source] Radiation sensitivity increases with proliferation-associated telomere dysfunction in nontransformed human epithelial cellsAGING CELL, Issue 4 2009David Soler Summary Epidemiological studies have demonstrated age differences among human adults in susceptibility to radiation, with cancer cases attributable to radiation being more frequent for older individuals at time of exposure. In addition to the notion that susceptibility increases because of progressive decline in DNA monitoring and immunosurveillance, telomere function is now emerging as a new and important factor in modulating cellular and organism sensitivity to ionizing radiation. The link between telomeres and radiosensitivity is well-documented in humans, but the causal events remain elusive. In this paper, it is shown that irradiated human epithelial cells with short dysfunctional telomeres derived from normal mammary gland display elevated DNA damage. An approach identifying the specific chromosomes with critically shortened telomeres in each donor has allowed us to conclude that short dysfunctional telomeres in human epithelial cells join radiation-induced DNA broken ends, thus interfering with their efficient repair. These findings argue against telomeres participating as sensors or transducers of DNA damage, as previously suggested. Rather, our current findings give support to the idea that dysfunctional telomeres, by acting as an additional joining option, reduce the repair fidelity of DNA broken-ends induced by radiation throughout the genome. In the mammary gland, age-dependent telomere attrition due to epithelial turnover, together with the accretion of checkpoint deficiencies, might render the accumulation of short dysfunctional telomeres. This implies that the risks associated with mammography screening could be higher than previously assumed. Our results have the possibility of imprinting a temporal dimension onto radiation sensitivity, namely, that shortened telomeres in aged cells may more easily compromise normal tissue function in the elderly. [source] Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: The nuclear medicine perspectiveJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2004Giuliano Mariani MD Abstract The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. 99mTc-labeled colloids with most of the particles in the 100,200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94,97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T1a-b breast cancers, with size ,1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients. J. Surg. Oncol. 2004;85:112,122. © 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||