Alterations in phosphoinositide metabolism associated with 17 beta-estradiol and growth factor treatment of MCF-7 breast cancer cells.
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 h 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) alpha-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 TGF alpha results in elevated PtdIns turnover and that chronic treatment increases growth rate. In contrast TGF beta is growth inhibitory and blocks estradiol-induced increases in PtdIns turnover. A phosphatidyl inositol 4,5-bisphosphate specific phospholipase-C activity has been identified and is elevated in association with estradiol treatment. These data are consistent with estradiol-induced autocrine growth factors, including TGF alpha, acting through the PtdIns turnover pathway as part of their mechanism of action.
Freter
C E
CE
Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
Lippman
M E
ME
Cheville
A
A
Zinn
S
S
Gelmann
E P
EP
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D006133:Growth Substances; D010716:Phosphatidylinositols; D011759:Pyrrolidines; D013876:Thiophenes; D004958:Estradiol; C025430:LY 117018