Andò S, Panno M L, Salerno M, Sisci D, Mauro L, Lanzino M, Surmacz E
Dipartimento di Biologia Cellulare, Universita' degli Studi della Calabria, Cosenza, Italy.
Biochem Biophys Res Commun. 1998 Dec 18;253(2):315-9. doi: 10.1006/bbrc.1998.9330.
Cross-talk between steroid hormones and polypeptide growth factors regulates the growth of hormone-responsive breast cancer cells. For example, in the MCF-7 human breast cancer cell line, insulin up-regulates estrogen receptor (ER) content and binding capacity. Since the insulin receptor (IR) substrate 1 (IRS-1) is one of the core signaling elements transmitting mitogenic and metabolic effects of insulin, we investigated whether IRS-1 is also required for the insulin-induced function of the ER. The effects of insulin on the ER were compared in MCF-7 cells and MCF-7-derived cell lines with decreased levels (by approximately 80%) of IRS-1 due to the expression of IRS-1 antisense RNA. The severe IRS-1 deficiency in MCF-7 cells was associated with (1) reduced mitogenic response to 20 ng/ml insulin and 10% calf serum (CS), but not to 1 nM estradiol (E2); (2) loss of insulin-E2 synergism; (3) up-regulation of ER protein expression and binding capacity; and (4) loss of insulin-induced regulation of ER tyrosine phosphorylation. In conclusion, the data confirm the existence of the IR-ER cross-talk and suggest that IRS-1-dependent signaling may contribute to the negative regulation of the ER expression and function in MCF-7 cells.
类固醇激素与多肽生长因子之间的相互作用调节着激素反应性乳腺癌细胞的生长。例如，在MCF-7人乳腺癌细胞系中，胰岛素上调雌激素受体（ER）的含量和结合能力。由于胰岛素受体（IR）底物1（IRS-1）是传递胰岛素促有丝分裂和代谢作用的核心信号元件之一，我们研究了IRS-1是否也是ER胰岛素诱导功能所必需的。在MCF-7细胞和由于IRS-1反义RNA表达而使IRS-1水平降低（约80%）的MCF-7衍生细胞系中，比较了胰岛素对ER的影响。MCF-7细胞中严重的IRS-1缺陷与以下情况相关：（1）对20 ng/ml胰岛素和10%小牛血清（CS）的促有丝分裂反应降低，但对1 nM雌二醇（E2）无此反应；（2）胰岛素-E2协同作用丧失；（3）ER蛋白表达和结合能力上调；（4）胰岛素诱导的ER酪氨酸磷酸化调节丧失。总之，这些数据证实了IR-ER相互作用的存在，并表明依赖IRS-1的信号传导可能有助于对MCF-7细胞中ER表达和功能的负调节。
