| Summary: | 碩士 === 中山醫學大學 === 免疫學研究所 === 96 === Insulin is a pleiotropic hormone, functioning in metabolism, proliferation, survival and gene expression. In mammary epithelial cells, insulin potentiates prolactin-induced expression of milk proteins and promotes cell survival. However, optimal insulin signaling requires cell adhesion to basement membrane (BM). Mammary cells contacting BM exhibit higher extents of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), whereas cells cultured on collagen I or plastic are insufficient in conducting this signaling event. Somehow tyrosine phosphorylation of insulin receptor is not affected. Here we further explore the underlying mechanism and find that IRS-1 expression is modulated by substratum. Higher levels of IRS-1 mRNA and protein are detected in cells cultured on BM compared to those cultured on plastic; but in the latter cells, inclusion of the calpain inhibitor ALLN substantially elevates levels of IRS-1 expression and IRS-1 tyrosine phosphorylation. Similar results are obtained by treatment of cells with the Rho kinase (Rok) inhibitor Y27632. Moreover, we found that expression of estrogen receptor-alpha (ERalpha) is also modulated by substratum in a similar fashion as expression of IRS-1 in that mammary cells cultured on BM display higher amount of ERalpha than those on plastic. Moreover, we found that expression of estrogen receptor-α (ERα) is also modulated by substratum in a similar fashion as expression of IRS-1 in that mammary cells cultured on BM display higher amount of ERα than those on plastic. Treatment of cells with β-estradiol increases level of IRS-1 expression in cells cultured on BM, whereas application of ICI182,780 exerts the opposite results. Taken together, our data suggest that Rok, calpain and ERα activity are involved in substratum-mediated regulation of IRS-1 expression, thereby affecting insulin signaling efficiency.
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