The effects of TGF-α and 17β-estradiol on polyphosphoinositide metabolism in MCF-7 breast cancer cells

Abstract

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.

Effects of oestradiol and tamoxifen on oxytocin-induced phospholipase C activation in human myometrial cells

“…Adding oestradiol in dextran-coated charcoal-treated-FCS medium without phenol red resulted in increased cell prolifera¬ tion and overall increased metabolism of polyphosphoinositides. This is also observed in oestrogen-positive cells (Schrey et al, 1992;Etindi et al, 1992). As in MCF-7 cells stimulated with bombesin (Schrey et al, 1992), oestradiol does not appear to exert a permissive effect on oxytocin action in myometrial cells, but positively affects the incorporation of [3H]inositol into inositol lipids.…”

Characterization of the Breast Cancer Susceptibility Gene BRCA2

“…In endometrial fibroblasts as well as selected malignant cell lines, E 2 stimulates the activity of PKC (22). Furthermore, in MCF-7 cells, synthesis of phosphatidylinositol and activation of phosphatidylinositol kinases can occur in response to E 2 treatment (23). ER itself can also act as a substrate for PKA.…”