Dickson R B, Huff K K, Spencer E M, Lippman M E
Endocrinology. 1986 Jan;118(1):138-42. doi: 10.1210/endo-118-1-138.
MCF-7 human breast cancer cells release polypeptides related to insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) into serum-free culture medium (CM). Treatment of MCF-7 cells with 17 beta-estradiol, which is required in vivo for MCF-7 tumor growth in the nude mouse and stimulates the MCF-7 growth rate in vitro, resulted in selectively enhanced growth factor activities in CM. Autostimulatory growth-promoting activity was elevated at least 2-fold, and EGF-like polypeptides were elevated 5-fold but IGF-I immunoreactivity was not elevated. Several species of estrogen-induced receptor-reactive EGF-like polypeptides, suggestive of high molecular weight transforming growth factor alpha, were detected after gel exclusion chromatography of CM extracted with 1 M acetic acid. A 30,000 mol wt peak of EGF receptor competing activity comigrated with a peak of autostimulatory and fibroblast-transforming activity. It is possible that estradiol stimulation of MCF-7 growth and/or tumor formation may depend on induction of EGF-related polypeptide growth factors. EGF-I- and EGF-related polypeptides may act together as autocrine or paracrine growth factors in breast cancer.
MCF-7人乳腺癌细胞可将与胰岛素样生长因子-I（IGF-I）和表皮生长因子（EGF）相关的多肽释放到无血清培养基（CM）中。用17β-雌二醇处理MCF-7细胞，17β-雌二醇在裸鼠体内是MCF-7肿瘤生长所必需的，且能在体外刺激MCF-7的生长速率，结果导致CM中的生长因子活性选择性增强。自刺激生长促进活性至少提高了2倍，EGF样多肽提高了5倍，但IGF-I免疫反应性未升高。在用1M乙酸提取的CM进行凝胶排阻色谱分析后，检测到几种雌激素诱导的受体反应性EGF样多肽，提示为高分子量转化生长因子α。一个分子量为30,000的EGF受体竞争活性峰与自刺激和成纤维细胞转化活性峰共迁移。雌二醇刺激MCF-7生长和/或肿瘤形成可能依赖于EGF相关多肽生长因子的诱导。EGF-I和EGF相关多肽可能在乳腺癌中共同作为自分泌或旁分泌生长因子起作用。
