Etindi R N, Manni A, Martel J
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Breast Cancer Res Treat. 1992;24(1):61-70. doi: 10.1007/BF01832359.
The mechanism by which transforming growth factor-alpha (TGF-alpha) stimulates breast cancer cell proliferation is largely unknown. Furthermore, its potential role as an autocrine effector of estradiol-17 beta (E2)-stimulated growth of hormone-dependent mammary tumors remains controversial. Transient changes in phosphatidylinositol (PI) turnover have been demonstrated in several tissues in response to growth factors. In these experiments, we tested the effects of TGF-alpha and E2 on PI metabolism in three MCF-7 breast cancer cell sublines (MCF-7B, MCF-7I, and MCF-7J). Although TGF-alpha was mitogenic in MCF-7I and MCF-7J cells, PI hydrolysis was stimulated by the growth factor only in the MCF-7I cells. In addition, the TGF-alpha effect was relatively modest, ranging from 23% to 42%. E2 effects on PI turnover were tested in the MCF-7B cells, which were the most sensitive to the proliferative effect of the hormone. E2 did not stimulate PI hydrolysis, whether or not the cells were labelled in the presence of the hormone. On the other hand, E2 did seem to stimulate de novo synthesis of phosphatidylinositol and induce activation of PI kinases. These results demonstrate that TGF-alpha-stimulated PI hydrolysis is modest and cell type dependent. At least under certain conditions, PI metabolism is not involved in the proliferative effects of TGF-alpha (MCF-7J) or E2 (MCF-7B). The role of increased PI synthesis in E2-stimulated MCF-7 cell growth remains to be established.
转化生长因子α（TGF-α）刺激乳腺癌细胞增殖的机制在很大程度上尚不清楚。此外，其作为雌二醇-17β（E2）刺激的激素依赖性乳腺肿瘤生长的自分泌效应器的潜在作用仍存在争议。已证实在几种组织中，磷脂酰肌醇（PI）周转会因生长因子而发生短暂变化。在这些实验中，我们测试了TGF-α和E2对三种MCF-7乳腺癌细胞亚系（MCF-7B、MCF-7I和MCF-7J）中PI代谢的影响。尽管TGF-α在MCF-7I和MCF-7J细胞中具有促有丝分裂作用，但只有在MCF-7I细胞中生长因子才能刺激PI水解。此外，TGF-α的作用相对较小，范围在23%至42%之间。在对激素增殖作用最敏感的MCF-7B细胞中测试了E2对PI周转的影响。无论细胞是否在激素存在的情况下进行标记，E2均未刺激PI水解。另一方面，E2似乎确实刺激了磷脂酰肌醇的从头合成并诱导了PI激酶的激活。这些结果表明，TGF-α刺激的PI水解作用较小且具有细胞类型依赖性。至少在某些条件下，PI代谢不参与TGF-α（MCF-7J）或E2（MCF-7B）的增殖作用。PI合成增加在E2刺激的MCF-7细胞生长中的作用仍有待确定。
