Huynh H, Yang X, Pollak M
Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.
J Biol Chem. 1996 Jan 12;271(2):1016-21. doi: 10.1074/jbc.271.2.1016.
MCF-7 human breast cancer cells are commonly used to model tissues responsive to estrogens and antiestrogens. We examined the effects of estradiol and the antiestrogen ICI 182780 on MCF-7 cell proliferation and insulin-like growth factor binding protein 3 (IGFBP-3) gene expression. ICI 182780-induced growth inhibition was associated with increased transcription of the IG-FBP-3 gene, increased IGFBP-3 mRNA abundance, and increased IGFBP-3 protein accumulation in the conditioned medium. The growth stimulatory effect of estradiol was associated with opposite effects, and the correlation between cellular proliferation and IGFBP-3 mRNA abundance was strong (r = -0.91). Recombinant IGFBP-3 inhibited basal and estradiol-stimulated MCF-7 cell proliferation, and an IGFBP-3 antisense oligodeoxynucleotide abolished antiestrogen-induced growth inhibition. These results provide evidence for an estradiol and antiestrogen-regulated IGFBP-3 growth inhibitory autocrine pathway in MCF-7 cells.
MCF-7人乳腺癌细胞常用于模拟对雌激素和抗雌激素有反应的组织。我们研究了雌二醇和抗雌激素ICI 182780对MCF-7细胞增殖及胰岛素样生长因子结合蛋白3（IGFBP-3）基因表达的影响。ICI 182780诱导的生长抑制与IGFBP-3基因转录增加、IGFBP-3 mRNA丰度增加以及条件培养基中IGFBP-3蛋白积累增加相关。雌二醇的生长刺激作用则与之相反，且细胞增殖与IGFBP-3 mRNA丰度之间的相关性很强（r = -0.91）。重组IGFBP-3抑制基础状态及雌二醇刺激的MCF-7细胞增殖，而IGFBP-3反义寡脱氧核苷酸消除了抗雌激素诱导的生长抑制。这些结果为MCF-7细胞中存在由雌二醇和抗雌激素调节的IGFBP-3生长抑制自分泌途径提供了证据。
