Home About us Contact
|
Home About us Contact | ||
|
|
||
MCF-7 Breast Cancer Cells (mcf-7 + breast_cancer_cell)
Selected AbstractsMethyl mercury influences growth-related signaling in MCF-7 breast cancer cellsENVIRONMENTAL TOXICOLOGY, Issue 1 2005Olga A. Sukocheva Abstract Environmental contaminants have been shown to alter growth-regulating signaling pathways through molecular mechanisms that are mainly unclear. Here we report that within a narrow concentration range (0.5,1 ,M) methyl mercury (MeHg) significantly stimulated growth of MCF-7 cells, induced Ca2+ mobilization, and activated extracellular signal,regulated kinase ½ (Erk1/2). MeHg modulated E2 -dependent stimulation of growth in a dose-dependent manner, although MeHg neither suppresses nor increases constitutive E2 metabolism. MeHg demonstrated weak estrogen receptor (ER),binding ability. However, long preincubation with antiestrogens LY156,758 and ICI164,384 decreased MeHg-induced foci formation, Ca2+ mobilization, and Erk1/2 activation, confirming involvement of ERs. The MeHg-induced increase in [Ca2+]i was observed to coincide with enhanced Erk1/2 phosphorylation. These data suggest that MeHg can significantly modulate the intracellular signaling environment in MCF-7 cells, resulting in a dose-dependent alteration of ER,mediated estrogenic capacity and therefore should be considered as a potential estrogen-disrupting compound. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 32,44, 2005. [source] Substances with estrogenic activity in effluents of sewage treatment plants in southwestern Germany.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2001Abstract The proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-Screen assay) was applied for quantitative determination of total estrogenic activity in 24-h composite effluent samples from 16 municipal and two industrial sewage treatment plants (STPs) in the state of Baden-Württemberg, southwestern Germany. The estrogenic efficacy relative to the positive control, 17,-estradiol, was between 26 and 74% (median, 48%) for the 16 municipal STPs. Estradiol equivalent concentrations (EEQs) were between 0.2 and 7.8 ng/L (median, 1.6 ng/L) and, thereby, were lower than those found in a pilot study, which revealed EEQs of greater than 10 ng/L in the effluents of two other STPs. The EEQs in 14 of the 16 effluent samples were very similar (0.9,3.3 ng/L), indicating a rather constant input of estrogenic substances via STPs into rivers. Additional activated charcoal filtration turned out to be very efficient in further eliminating estrogenic activity from effluents. The EEQs of the E-Screen assay and those calculated from the results of extensive chemical analysis using the estradiol equivalency factors determined for 13 natural and synthetic estrogenic substances were comparable for most of the effluent samples. 17,-Estradiol, 17,-ethinylestradiol, and, to a lesser extent, estrone contributed to 90% or more of the EEQ value. [source] Progestin upregulates G-protein-coupled receptor 30 in breast cancer cellsFEBS JOURNAL, Issue 10 2002Tytti M. Ahola A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate (MPA). A transcript of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestin-specific primary target gene, which was enhanced by progesterone and different progestins, but not by dihydrotestosterone or dexamethasone, and which was abrogated by antiprogestin RU486. The dose-dependent and time-dependent increase in GPR30 mRNA expression correlated with MPA-induced growth inhibition in MCF-7 cells. Additionally, GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines. The ERK1/ERK2 pathway is capable of inducing progesterone receptor-dependent and ligand-dependent transcription. Thus we sought to establish whether different MAPK pathway inhibitors affect progestin-induced GPR30 mRNA regulation. The regulation of GPR30 was independent of ERK pathway activation, but the p38 pathway inhibitor induced GPR30 expression, which suggested a potential gene regulation pathway. These data demonstrate a new progestin target gene, the expression of which correlates with growth inhibition. [source] Generic Strategy of Preparing Fluorescent Conjugated-Polymer-Loaded Poly(DL -lactide- co -Glycolide) Nanoparticles for Targeted Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 22 2009Kai Li Abstract A general strategy for the preparation of highly fluorescent poly(DL-lactide- co -glycolide) (PLGA) nanoparticles (NPs) loaded with conjugated polymers (CPs) is reported. The process involves encapsulation of organic-soluble CPs with PLGA using a modified solvent extraction/evaporation technique. The obtained NPs are stable in aqueous media with biocompatible and functionalizable surfaces. In addition, fluorescent properties of the CP-loaded PLGA NPs (CPL NPs) could be fine-tuned by loading different types of CPs into the PLGA matrix. Four types of CPL NPs are prepared with a volume-average hydrodynamic diameter ranging from 243 to 272,nm. The application of CPL NPs for bio-imaging is demonstrated through incubation with MCF-7 breast cancer cells. Confocal laser scanning microscopy studies reveal that the CPL NPs are internalized in cytoplasm around the nuclei with intense fluorescence. After conjugation with folic acid, cellular uptake of the surface-functionalized CPL NPs is greatly enhanced via receptor-mediated endocytosis by MCF-7 breast cancer cells, as compared to that for NIH/3T3 fibroblast cells, which indicates a selective targeting effect of the folate-functionalized CPL NPs in cellular imaging. The merits of CPL NPs, such as low cytotoxicity, high fluorescence, good photostability, and feasible surface functionalization, will inspire extensive study of CPL NPs as a new generation of probes for specific biological imaging and detection. [source] Experimental design comparison of studies evaluating doxorubicin nanoparticles in breast cancer therapyHUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES, Issue 3 2008Farman A. Moayed Background The unique properties of nanoparticles (NP) qualify these colloidal systems for a wide range of medical applications, including diagnosis and treatment. Particularly in cancer therapy, NP have significantly enhanced the potential of conventional imaging, radiotherapy, and chemotherapy and, consequently, offered new avenues for early interventions. So far, breast cancer has been one of the most studied cancer types with NP research, which can benefit the occupational breast cancer for the increasing number of women in the labor force in industry. Objectives The objective of this study is to compare the experimental designs of preclinical studies that assessed the effect of doxorubicin NP (DOX-NP) on the estrogen-dependent MCF-7 breast cancer cell line using a recently established quantitative Experimental Appraisal Instrument (ExpAI). Methods A systematic review of research articles published between August 2004 and August 2005 on NP and breast cancer treatment with doxorubicin was performed using various online databases and indexes available through the University of Cincinnati. Restrictive inclusion and exclusion criteria were defined leading to selection of four relevant articles that used comparable experimental designs. Critical appraisal of those studies was performed by five independent assessors using the ExpAI version 2.0 and the results were summarized in a table of evidence. Results The study design in the selected articles was either between groups or mixed, with sample sizes varying from n = 3,6, and the evaluation of the effect of DOX-NP either in vitro or in vivo. The cytotoxic drug doxorubicin was the input variable in all studies, whereas different end points such as pharmacokinetic parameters, cytotoxicity surrogates (e.g., growth inhibition, mitochondrial activity), and quantitative analysis of messenger RNA were used as output variables. Conclusions Although the articles assessed in this article were preclinical experimental studies, the results showed that doxorubicin NP drugs can be used effectively to enhance the delivery process in MCF-7 breast cancer cells by increasing the circulation time and targeting the tumor tissues. Considering the rising number of women in the labor force and the risk of occupational breast cancer, it can be concluded that DOX-NP may potentially be used as an effective anticancer drug on humans, but further research and studies are required to understand how DOX-NP drugs might react in the human body before using it on breast cancer patients. © 2008 Wiley Periodicals, Inc. [source] A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2005Liliane Goetsch Abstract Interaction of insulin-like growth factor receptor I (IGF-IR) with its ligands has been reported to induce cell proliferation, transformation and blockade of cell apoptotic functions. IGF-IR is overexpressed on numerous tumor cell types and its blockade could be of importance for anti-cancer therapy. We have generated a humanized anti-IGF-IR antibody h7C10 that blocks in vitro IGF-I and IGF-II-induced cell proliferation of MCF-7 breast cancer cells. Analysis of the IGF-I transduction cascade demonstrated that the humanized anti-IGF-IR antibody and its murine parental form block IGF-I-induced tyrosine phosphorylation, both its ,-chain and IRS-1 tyrosine phosphorylation. This presumably leads to cell cycle arrest and, consequently, growth inhibition. Treatment of nude mice bearing either human breast cancer cells (MCF-7) or non small lung cancer cells (A549) with h7C10, or its murine parental form 7C10, inhibited significantly tumor growth. An almost complete inhibition of A549 tumor growth was observed when mice were treated with the anti-IGF-IR antibody combined with either a chemotherapeutic agent, Vinorelbine or an anti-epidermal growth factor receptor (EGFR) antibody, 225. Combined therapy prolonged significantly the life span of mice in an orthotopic in vivo model of A549; the combination of the anti-IGF-IR antibody with an anti-EGFR antibody was superior to the Vinorelbine combination. The present results indicate that the humanized anti-IGF-IR antibody h7C10 has a great potential for cancer therapy when combined with either a chemotherapeutic agent or an antibody that targets other growth factor receptors, such as the epidermal growth factor receptor. [source] miR-20b modulates VEGF expression by targeting HIF-1, and STAT3 in MCF-7 breast cancer cells,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Sandra Cascio MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of different genes, including genes involved in cancer progression. A functional link between hypoxia, a key feature of the tumor microenvironment, and miRNA expression has been documented. We investigated whether and how miR-20b can regulate the expression of vascular endothelial growth factor (VEGF) in MCF-7 breast cancer cells under normoxic and hypoxia-mimicking conditions (CoCl2 exposure). Using immunoblotting, ELISA, and quantitative real-time PCR, we demonstrated that miR-20b decreased VEGF protein levels at 4 and 24,h following CoCl2 treatment, and VEGF mRNA at 4,h of treatment. In addition, miR-20b reduced VEGF protein expression in untreated cells. Next, we investigated the molecular mechanism by which pre-miR-20b can affect VEGF transcription, focusing on hypoxia inducible factor 1 (HIF-1) and signal transducer and activator of transcription 3 (STAT3), transcriptional inducers of VEGF and putative targets of miR-20b. Downregulation of VEGF mRNA by miR-20b under a 4,h of CoCl2 treatment was associated with reduced levels of nuclear HIF-1, subunit and STAT3. Chromatin immunoprecipitation (ChIP) assays revealed that HIF-1,, but not STAT3, was recruited to the VEGF promoter following the 4,h of CoCl2 treatment. This effect was inhibited by transfection of cells with pre-miR-20b. In addition, using siRNA knockdown, we demonstrated that the presence of STAT3 is necessary for CoCl2 -mediated HIF-1, nuclear accumulation and recruitment on VEGF promoter. In summary, this report demonstrates, for the first time, that the VEGF expression in breast cancer cells is mediated by HIF-1 and STAT3 in a miR-20b-dependent manner. J. Cell. Physiol. 224:242,249, 2010 © 2010 Wiley-Liss, Inc. [source] Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugateJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2007Wjatschesslaw A. Wlassoff A new approach to the treatment of cancer is suggested, based on the innate overproduction of hydrogen peroxide in cancer cells. Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam-Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF-7 breast cancer cells treated with Tam-Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. These results show that the hydrogen peroxide overproduced in tumour cells can serve as a prodrug for the treatment of cancer. [source] Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatoninJOURNAL OF PINEAL RESEARCH, Issue 4 2000Prahlad T. Ram The estrogen receptor (ER)-positive MCF-7 human breast cancer cell line has been used extensively for the study of estrogen-responsive human breast cancer. However, various levels of estrogen responsiveness have been described in different stocks of MCF-7 cells. Because we have previously shown that the pineal hormone, melatonin, inhibits proliferation of MCF-7 cells and can modulate ER expression and transactivation, we investigated if various stocks of MCF-7 cells exhibit a differential responsiveness to the anti-proliferative effects of melatonin and the possible mechanisms involved. The MCF-7 stocks (M, O, H) were examined for: (1) mitogenic response to estradiol; (2) steady-state ER mRNA levels; (3) expression of the mt1 melatonin membrane receptor; (4) growth inhibition by melatonin; and (5) melatonin's modulation of expression of the ER and the estrogen-regulated genes, PgR, TGF, and pS2. For all of these parameters, there was a stock-specific response which showed: MCF-7M>MCF-7O>MCF-7 H. These results demonstrate that there are significant differences in the responsiveness of various stocks of MCF-7 breast cancer cells to the growth-inhibitory effects of melatonin which can be correlated with both the level of ER mRNA expression and the degree of estrogen-responsiveness. These findings suggest that not only may these differences have some impact on the cells' estrogen-response pathway, but also that the primary growth-inhibitory effects of melatonin are transduced through the membrane-associated G-protein coupled mt1 melatonin receptor. [source] Retinoids and retinoic acid receptors regulate growth arrest and apoptosis in human mammary epithelial cells and modulate expression of CBP/p300MICROSCOPY RESEARCH AND TECHNIQUE, Issue 1 2002Eric C. Dietze Abstract Retinoids and retinoic acid receptors (RARs) are important mediators of normal epithelial cell homeostasis. To assess the role of retinoids and RARs in regulating growth arrest and apoptosis in benign and malignant mammary epithelial cells, two model systems were developed: 1) RAR function was suppressed in retinoid-sensitive normal human mammary epithelial cells (HMECs) by the dominant-negative retinoic acid receptor, RAR,403 (DNRAR), and 2) retinoid-resistant MCF-7 breast cancer cells were transduced with a functional RAR,2. Inhibition of RAR function by the DNRAR in HMECs resulted in retinoid-resistance, increased proliferation, and dysregulated growth when cells were cultured in reconstituted extracellular matrix (rECM). Expression of RAR,2 in MCF-7 cells resulted in sensitivity to retinoid-induced growth arrest and apoptosis. The CREB-binding protein (CBP) and the homologous protein p300 are tightly regulated, rate-limiting integrators of diverse signaling pathways and are recruited during retinoid-mediated transcriptional activation. The relationship between retinoid receptor expression, growth regulation, and transcriptional regulation of CBP/p300 is poorly understood. Inhibition of RAR function in HMECs by DNRAR suppressed expression of CBP/p300 and expression of RAR,2 in MCF-7 cells promoted induction of CBP/p300 when cells were treated with 1.0 ,M all- trans -retinoic acid (ATRA). These results suggest that ATRA and RARs regulate growth arrest of HMECs and modulate CBP/p300 protein expression. Since CBP and p300 are normally present in limiting amounts, their regulation by ATRA and RARs may be an important element in the control of transcriptional activation of genes regulating growth arrest and apoptosis. Microsc. Res. Tech. 59:23,40, 2002. © 2002 Wiley-Liss, Inc. [source] Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activationMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2010Rosa Sirianni Abstract The growth of many breast tumors is stimulated by estradiol (E2), which activates a classic mechanism of regulation of gene expression and signal transduction pathways inducing cell proliferation. Polyphenols of natural origin with chemical similarity to estrogen have been shown to interfere with tumor cell proliferation. The aim of this study was to investigate whether hydroxytyrosol (HT) and oleuropein (OL), two polyphenols contained in extra-virgin olive oil, can affect breast cancer cell proliferation interfering with E2-induced molecular mechanisms. Both HT and OL inhibited proliferation of MCF-7 breast cancer cells. Luciferase gene reporter experiments, using a construct containing estrogen responsive elements able to bind estrogen receptor alpha (ER,) and the study of the effects of HT or OL on ER, expression, demonstrated that HT and OL are not involved in ER,-mediated regulation of gene expression. However, further experiments pointed out that both OL and HT determined a clear inhibition of E2-dependent activation of extracellular regulated kinase1/2 belonging to the mitogen activating protein kinase family. Our study demonstrated that HT and OL can have a chemo-preventive role in breast cancer cell proliferation through the inhibition of estrogen-dependent rapid signals involved in uncontrolled tumor cell growth. [source] Nested effects models for learning signaling networks from perturbation dataBIOMETRICAL JOURNAL, Issue 2 2009Holger Fröhlich Abstract Targeted gene perturbations have become a major tool to gain insight into complex cellular processes. In combination with the measurement of downstream effects via DNA microarrays, this approach can be used to gain insight into signaling pathways. Nested Effects Models were first introduced by Markowetz et al. as a probabilistic method to reverse engineer signaling cascades based on the nested structure of downstream perturbation effects. The basic framework was substantially extended later on by Fröhlich et al., Markowetz et al., and Tresch and Markowetz. In this paper, we present a review of the complete methodology with a detailed comparison of so far proposed algorithms on a qualitative and quantitative level. As an application, we present results on estimating the signaling network between 13 genes in the ER-, pathway of human MCF-7 breast cancer cells. Comparison with the literature shows a substantial overlap. [source] [Pt(O,O,-acac)(,-acac)(DMS)], a new Pt compound exerting fast cytotoxicity in MCF-7 breast cancer cells via the mitochondrial apoptotic pathwayBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2008A Muscella British Journal of Pharmacology (2008) 153, 175; doi:10.1038/sj.bjp.0707646 [source] Type II estrogen binding site agonist:CHIRALITY, Issue 8 2003Synthesis, biological evaluation of the enantiomers of methyl-para-hydroxyphenyllactate (MeHPLA) Abstract A high-affinity ligand for the type II estrogen binding site (EBS) was identified. Methyl para-hydroxyphenyllactate (MeHPLA) was observed to suppress the cellular proliferation of estrogen-sensitive MCF-7 breast cancer cells in vitro and to suppress the growth of rat uteri in vivo. The high affinity of MeHPLA for the type II EBS suggests that this interaction is responsible for the observed suppression of cell growth. In this study, the enantiomers of MeHPLA were synthesized and separated by three methods and evaluated for biological activity. When the methods were compared, it was found that the method using an optically pure amine to form the diastereomers of the enantiomers gave the superior yield. Binding studies for the enantiomers to the type II EBS showed that the S-MeHPLA had a higher affinity for the binding site. However, higher binding affinity did not translate into superior cell growth suppression. Both enantiomers suppressed cell growth equally. Chirality 15:674,679, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||||||||