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Epithelial Origin (epithelial + origin)
Selected AbstractsThe ,II isotype of tubulin is present in the cell nuclei of a variety of cancersCYTOSKELETON, Issue 2 2004I-Tien Yeh Abstract Tubulin, the subunit protein of microtubules, has generally been thought to be exclusively a cytoplasmic protein in higher eukaryotes. We have previously shown that cultured rat kidney mesangial cells contain the ,II isotype of tubulin in their nuclei in the form of an ,,II dimer [Walss et al., 1999: Cell Motil. Cytoskeleton 42:274,284, 1999]. More recently, we examined a variety of cancerous and non-cancerous cell lines and found ,II in the nuclei of all of the former and only a few of the latter (Walss-Bass et al., 2002: Cell Tissue Res. 308:215,223]. In order to determine if ,II -tubulin occurs in the nuclei of actual cancers as well as in cancer cell lines, we used the immunoperoxidase method to look for nuclear ,II in a variety of tumors excised from 201 patients. We found that 75% of these tumors contain ,II in their nuclei. Distribution of nuclear ,II was highly dependent on the type of cancer, with 100% of the colon and prostate cancers, but only 19% of the skin tumors, having nuclear ,II. Nuclear ,II was particularly marked in tumors of epithelial origin, of which 83% showed nuclear ,II, in contrast to 54% in tumors of non-epithelial origin. In many cases, ,II staining occurred very strongly in the nuclei and not in the cytoplasm; in other cases, ,II was present in both. In many cases, particularly metastases, otherwise normal cells adjacent to the tumor also showed nuclear ,II, suggesting that cancer cells may influence nearby cells to synthesize ,II and localize it to their nuclei. Our results have implications for the diagnosis, biology, and chemotherapy of cancer. Cell Motil. Cytoskeleton 57:96,106, 2004. © 2004 Wiley-Liss, Inc. [source] Expression and distribution of distinct variants of E-MAP-115 during proliferation and differentiation of human intestinal epithelial cellsCYTOSKELETON, Issue 4 2003Marie-Thérèse Vanier Abstract Epithelial cell proliferation and differentiation occur concomitant with striking remodeling of the cytoskeleton. Microtubules (MTs) play important roles in these processes, during which the MTs themselves are reorganized and stabilized by microtubule-associated proteins (MAPs). Among the proteins classified as structural MAPs, E-MAP-115 (also named ensconsin) is preferentially expressed in cells of epithelial origin. The aims of this study were, first, to determine if E-MAP-115, like other MAPs, is expressed as different isoforms during differentiation and, second, to perform a detailed analysis of the expression and distribution of any E-MAP-115 variants detected in intestinal epithelial cells during their polarization/differentiation. It was our expectation that these data would help us to develop hypotheses concerning the role of this MAP in epithelial development. We report the expression of three E-MAP-115 transcripts encoding isoforms of 115, 105, and 95 kDa; two display an expression gradient inverse to the third one as Caco-2 cells progress from proliferation through the stages of differentiation. To monitor the proteins produced from each transcript, we used purified polyclonal antibodies against synthetic peptides contained within the 115, 105, and 95 kDa isoforms to assay proliferating and differentiating CaCo-2 cells. Our results indicate that the expression and MT-binding capacity of the 115, 105, and 95 kDa isoforms vary upon proliferation/differentiation of the cells. E-MAP-115 proteins colocalize with MTs in proliferative and differentiated Caco-2 cells; in vivo, they are expressed in both crypt and villus epithelial cells where they are mainly concentrated at the apical pole of the cells. Cell Motil. Cytoskeleton 55:221,231, 2003. © 2003 Wiley-Liss, Inc. [source] Transforming growth factor-,1 expression is up-regulated in maturation-stage enamel organ and may induce ameloblast apoptosisEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2009Masahiro Tsuchiya Transforming growth factor-,1 (TGF-,1) regulates a variety of cellular responses that are dependent on the developmental stage and on the origins of the cell or the tissue. In mature tissues, and especially in tissues of epithelial origin, TGF-,1 is generally considered to be a growth inhibitor that may also promote apoptosis. The ameloblast cells of the enamel organ epithelium are adjacent to and responsible for the developing enamel layer on unerupted teeth. Once the enamel layer reaches its full thickness, the tall columnar secretory-stage ameloblasts shorten, and a portion of these maturation-stage ameloblasts become apoptotic. Here we investigate whether TGF-,1 plays a role in apoptosis of the maturation-stage ameloblasts. We demonstrate in vitro that ameloblast lineage cells are highly susceptible to TGF-,1-mediated growth arrest and are prone to TGF-,1-mediated cell death/apoptosis. We also demonstrate in vivo that TGF-,1 is expressed in the maturation-stage enamel organ at significantly higher levels than in the earlier secretory-stage enamel organ. This increased expression of TGF-,1 correlates with an increase in expression of the enamel organ immediate-early stress-response gene and with a decrease in the anti-apoptotic Bcl2 : Bax expression ratio. We conclude that TGF-,1 may play an important role in ameloblast apoptosis during the maturation stage of enamel development. [source] Regulation of Sprouty2 stability by mammalian Seven-in-Absentia homolog 2,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2007Robert J. Nadeau Abstract Mammalian Sprouty (Spry) gene expression is rapidly induced upon activation of the FGF receptor signaling pathway in multiple cell types including cells of mesenchymal and epithelial origin. Spry2 inhibits FGF-dependent ERK activation and thus Spry acts as a feedback inhibitor of FGF-mediated proliferation. In addition, Spry2 interacts with the ring-finger-containing E3 ubiquitin ligase, c-Cbl, in a manner that is dependent upon phosphorylation of Tyr55 of Spry2. This interaction results in the poly-ubiquitination and subsequent degradation of Spry2 by the proteasome. Here, we describe the identification of another E3 ubiquitin ligase, human Seven-in-Absentia homolog-2 (SIAH2), as a Spry2 interacting protein. We show by yeast two-hybrid analysis that the N-terminal domain of Spry2 and the ring finger domain of SIAH2 mediated this interaction. Co-expression of SIAH2 resulted in proteasomal degradation of Spry1, 2, and to a lesser extent Spry4. The related E3 ubiquitin-ligase, SIAH1, had little effect on Spry2 protein stability when co-expressed. Unlike c-Cbl-mediated degradation of Spry2, SIAH2-mediated degradation was independent of phosphorylation of Spry2 on Tyr55. Spry2 was also phosphorylated on Tyr227, and phosphorylation of this residue was also dispensable for SIAH2-mediated degradation of Spry2. Finally, co-expression of SIAH2 with Spry2 resulted in a rescue of FGF2-mediated ERK phosphorylation. These data suggest a novel mechanism whereby Spry2 stability is regulated in a manner that is independent of tyrosine phosphorylation, and provides an addition level of control of Spry2 protein levels. J. Cell. Biochem. 100: 151,160, 2007. © 2006 Wiley-Liss, Inc. [source] Expression of cytokeratin subtypes in intraepidermal malignancies: a guide for differentiationJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2006Figen Aslan Background:, Among intraepidermal malignancies of epithelial origin, Bowen's disease, bowenoid actinic keratosis (BAK), intraepidermal malignant eccrine poroma (MEP), and Paget's disease may pose diagnostic difficulties. Methods:, Histologic features and immunohistochemical profiles of 24 cases of Bowen's disease, 21 cases of BAK, 18 cases of intraepidermal MEP, and 11 cases of Paget's disease were analyzed. Results:, Using multivariate logistic regression test, multinuclear giant cells and solar degeneration were found to be the only histologic parameters of diagnostic help. On the other hand, a widespread positive reaction for CK 5/8, CK 7, CK 19, and negative reaction for CK 10, was a helpful feature in the differentiation of Paget's disease from Bowen's disease and BAK. The widespread and strong expression of CK 10 was seen in almost all cases of Bowen's disease in contrast to BAK. The widespread expression of CK 5/8 and CK 7, and negative reaction for CK 10, was in favor of Paget's disease, compared to intraepidermal MEP. On the other hand, widespread expression of CK 19 was a common finding in intraepidermal MEP, in contrast to Bowen's disease. Conclusion:, An immunohistochemical panel may provide significant hints on the differentiation of common intraepidermal malignancies, especially in problematic cases. [source] Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human ,,-T cells: Implications in the design of ,,-T-cell-based immunotherapies for pancreatic cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009Zhiyong Liu Abstract Background and Aims:, ,,-T cells can recognize and kill malignant cells, particularly those of epithelial origin, through mechanisms which do not require the recognition of tumor-specific antigens (innate immune response). This natural ability of ,,-T cells to kill tumor cells in a tumor antigen-independent manner provides a strong rationale for developing clinical trials designed to exploit the innate antitumor properties of ,,-T cells. Methods:,In vitro studies were carried out to asses the sensitivity of pancreatic cancer cells (MIA PaCa2, BxPC-3, PANC-1) to killing by ex vivo expanded human ,,-T cells. Results:, The capacity of ,,-T cells to bind to as well as to kill pancreatic cancer cells correlated with the degree of surface expression of key intercellular adhesion molecules (ICAM) present on pancreatic cancer cells. Moreover, pancreatic cancer cells expressing neither ICAM-1 nor ICAM-2 were bound poorly by ,,-T cells and were found to be resistant to ,,-T-cell killing. However, upon transfection of resistant cells with ICAM-1 or ICAM-2, ,,-T cells were then able to bind to and subsequently kill these cells. Conclusion:,In vitro, the expression of ICAM-1 or ICAM-2 on human pancreatic cancer cells is critically important in determining the extent to which these cells are sensitive to killing by human ,,-T cells. Accordingly, in ongoing and future clinical studies using ,,-T cells for the treatment of a variety of epithelial-derived solid tumors,including pancreatic cancer,interventions intended to modulate ICAM expression on tumor cells may become important adjuncts to ,,-T-cell-based immunotherapies. [source] In Vivo and In Vitro Evidence of the Involvement of CXCL1, a Keratinocyte-Derived Chemokine, in Equine LaminitisJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2009R.R. Faleiros Background: C-X-C motif ligand 1 (CXCL1) is an important chemokine of epithelial origin in rodents and humans. Objectives: To assess in vivo and in vitro the regulation of CXCL1 in equine laminitis. Animals: Twenty adult horses. Methods: Real-time quantitative polymerase chain reaction (PCR) was used to assess expression of CXCL1 in samples of laminae, liver, skin, and lung from the black walnut extract (BWE) model of laminitis, and in cultured equine epithelial cells (EpCs). Tissue was obtained from control animals (CON, n = 5), and at 1.5 hours (early time point [ETP] group, n = 5), at the onset of leukopenia (developmental time point [DTP] group, n = 5), and at the onset of lameness (LAM group, n = 5) after BWE administration. EpCs were exposed to Toll-like/Nod receptor ligands, oxidative stress agents, and reduced atmospheric oxygen (3%). In situ PCR was used to localize the laminar cell types undergoing CXCL1 mRNA expression. Results: Increases in laminar CXCL1 mRNA concentrations occurred in the ETP (163-fold [P= .0001]) and DTP groups (21-fold [P= .005]). Smaller increases in CXCL1 expression occurred in other tissues and organs. In cultured EpCs, increases (P < .05) in CXCL1 mRNA concentration occurred after exposure to lipopolysaccharide (LPS [28-fold]), xanthine/xanthine oxidase (3.5-fold), and H2O2 (2-fold). Hypoxia enhanced the LPS-induced increase in CXCL1 mRNA (P= .007). CXCL1 gene expression was localized to laminar EpCs, endothelial cells, and emigrating leukocytes. Conclusion and Clinical Importance: These findings indicate that CXCL1 plays an early and possibly initiating role in neutrophil accumulation in the BWE laminitis model, and that laminar keratinocytes are an important source of this chemokine. New therapies using chemokine receptor antagonists may be indicated. [source] Cyclooxygenase-2 expression and connection with tumor recurrence and histopathologic parameters in gastrointestinal stromal tumorsAPMIS, Issue 11 2009HÜSEYIN KEMAL TÜRKÖZ Tissue cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin synthesis and has been shown to have roles in carcinogenesis and tumor progression. Evaluation of COX-2 overexpression in malignancies has been performed mostly on tumors of epithelial origin, and little is known about its presence in mesenchymal tumors, especially gastrointestinal stromal tumors (GIST). COX-2 has been reported to be widely expressed in GIST and has been suggested as a potential diagnostic marker. We evaluated the overexpression and roles of COX-2 in tumorigenesis in GIST with regard to its relation to prognostic parameters and tumor recurrence. We studied the presence of COX-2 expression immunohistochemically and its relation to clinicopathologic prognostic variables in 41 cases of GIST. COX-2 was overexpressed in 21 (51%) of 41 tumors. The extent of overexpression was greater in tumors that recurred after surgical resection. COX-2 overexpression was also higher in tumors with coagulative necrosis, high mitotic index and an infiltrative pattern of growth. The observation of greater COX-2 expression levels in GIST with unfavorable histopathologic variables is contrary to previous reports and consistent with the reported roles of COX-2 in carcinogenesis of epithelial malignancies. [source] Detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in nongenital seborrhoeic keratosisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2004Y-H. Li Summary Background, DNA of epidermodysplasia verruciformis (EV)-associated human papillomaviruses (HPVs) has been widely detected in lesions of malignant skin tumours, benign tumours and other proliferative diseases of epithelial origin. Objectives, To investigate the presence of EV-associated HPV DNA in nongenital seborrhoeic keratosis (SK) and to elucidate the prevalence of distinct HPV genotypes. Methods, We investigated HPV DNA in 55 nongenital SK biopsies, which were compared with 48 normal skin biopsies (healthy controls) using a nested polymerase chain reaction (PCR) using consensus primers CP65/CP70 and CP66/CP69. The positive PCR products were retracted and used to prepare recombination clones with T-vector. Distinct clones were analysed with endonucleases, and HPV genotypes were identified by direct sequencing. Results, EV-associated HPV DNA was detected in 42 of 55 (76%) nongenital SK biopsies vs. only 13 of 48 (27%) healthy controls (,2 = 22·087; P < 0·005). The prevalence was higher in patients with more than five lesions than in those with only one lesion (P < 0·05). Ten distinct HPV genotypes were detected in the nongenital SK biopsies: HPV 20, 23, 5, renal transplant recipient (RTR) X7, HPV 17, 37, 17b, RTRX4, RTRX4b and strain SK3. HPV 20 was found in 26 of 42 (62%) positive specimens, followed by HPV 23 (11 of 42, 26%) and HPV 5 (six of 42, 14%). Existence of multiple HPV genotypes was observed in 12 of 42 (29%) positive specimens. In healthy controls, five genotypes of EV-associated HPV (HPV 20, 23, 5, 17 and RTRX4) were detected, with the same predominant genotype of HPV 20 (five of 13, 38%). Several distinct HPV genotypes were found to coexist in four of 13 (31%) positive specimens. Conclusions, This study provides some evidence that EV-associated HPVs might play a part in the pathogenesis of nongenital SK. [source] | |||||||||||||