Steady-state levels of phosphatidyl inositol (PtdIns) turnover are examined in MCF-7 human breast cancer cells in response to estradiol treatment. Elevated levels of PtdIns are observed 12-24 hr after estradiol treatment, occur at estradiol concentrations as low as 10-12 M, and are competitively blocked by the antiestrogen LY117018. MCF-7 cells secrete a transforming growth factor (TGF) α-like material which can partly replace estradiol in conferring tumorgenicity in nude mice. We show that acute or chronic treatment of MCF-7 cells with TGFα results in elevated PtdIns turnover and that chronic treatment increases growth rate. In contrast TGFβ is growth inhibitory and blocks estradiol-induced increases in PtdIns turnover. A phosphatidyl inositol 4,5-bisphosphate specific phospolipase-C activity has been identified and is elevated in association with estradiol treatment. These data are consistent with estradiol-induced autocrine growth factors, including TGFα, acting through the PtdIns turnover pathway as part of their mechanism of action.
ASJC Scopus subject areas
- Molecular Biology