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Human Breast Epithelial Cells (human + breast_epithelial_cell)
Selected AbstractsRoles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras -transformed human breast epithelial cellsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Hye-Jung Kang Abstract Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras -transformed cells of a common origin: parental (MCF10A) and H- ras -transformed (H- ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H- ras -transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H - ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H- ras -transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras -downstream signaling molecules in ras -activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis. © 2002 Wiley-Liss, Inc. [source] TCDD causes suppression of growth and differentiation of MCF10A, human mammary epithelial cells by interfering with their insulin receptor signaling through c-Src kinase and ERK activationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2005Sujin Park Abstract One of the proposed mechanisms of carcinogenic action of TCDD (=dioxin) on breast cells is that it causes significant inhibition of proper differentiation of mammary duct epithelial cells and thereby increases the number of terminal end buds, which are susceptible to other carcinogens (Fenton et al., Toxicol Sci 2002;67:63,74; Brown et al., Carcinogenesis 1998; 19:1623,1629; Lamartiniere, J Mammary Gland Biol Neoplasia 2002;7:67,76). To address this topic, we selected MCF10A, a line of immortalized normal human breast epithelial cells as an in vitro model. An initial effort was made to optimize the cultural condition of MCF10A cells to promote the cell differentiation effect of insulin. Under this condition, TCDD clearly antagonized the action of insulin only in the presence of cholera toxin that is known to promote the differentiation of normal human breast epithelial cells. To test the hypothesis that TCDD-induced c-Src kinase activation is casually related to this compound's antagonistic action against insulin, we treated MCF10A cells with two c-Src blocking agents, an anti-Src antisense oligonucleotides blocker and a known specific inhibitor of c-Src kinase, PP-2 and studied the effect of insulin and TCDD on cell proliferation. The results showed that, in cells treated with either of these two c-Src blocking agents, the antagonistic effect of TCDD disappeared. It was also found that agents which specifically block the activation of ERK could also abrogate the action of TCDD to suppress insulin signaling. Together, these results indicate that the mechanism of the antagonistic action of TCDD on insulin signaling is mainly mediated through c-Src signaling through activation of ERK. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:322,331, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20040 [source] Precancerous carcinogenesis of human breast epithelial cells by chronic exposure to benzo[a]pyreneMOLECULAR CARCINOGENESIS, Issue 5 2008Nalin Siriwardhana Abstract To understand carcinogenesis of human breast epithelial cells induced by chronic exposure to environmental pollutants, we studied biological and molecular changes in progression of cellular carcinogenesis induced by accumulated exposures to the potent environmental carcinogen benzo[a]pyrene (B[a]P). Increasing exposures of human breast epithelial MCF10A cells to B[a]P at picomolar concentrations resulted in cellular transformation from a noncancerous stage to precancerous substages, in which cells acquired the cancerous abilities of a reduced dependence on growth factors, anchorage-independent growth, and disruption in acini formation on reconstituted basement membranes. Using cDNA microarrays, we detected seven upregulated genes related to human cancers in B[a]P-transformed MCF10A cells. Using this model, we verified that green tea catechin significantly (P,<,0.05) suppressed B[a]P-induced carcinogenesis. Our studies indicate that this cellular model may serve as a cost-efficient, in vitro system, mimicking the chronic carcinogenesis of breast cells that likely occurs in early stages of carcinogenesis in vivo, to identify agents that inhibit cellular carcinogenesis. © 2007 Wiley-Liss, Inc. [source] | ||||||||||