The effects of TGF-alpha and 17 beta-estradiol on polyphosphoinositide metabolism in MCF-7 breast cancer cells.
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.
Etindi
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RN
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Manni
A
A
Martel
J
J
D001943:Breast Neoplasms / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D010716:Phosphatidylinositols; D016211:Transforming Growth Factor alpha; D000001:Calcimycin; D004958:Estradiol