Heterologous regulation of inositol lipid hydrolysis in human breast cancer cells by oestradiol 17 beta, bombesin and fluoroaluminate.
Inositol lipid turnover has been implicated in the action of oestradiol 17 beta and bombesin-related peptides on the human breast cancer cell line MCF-7. In the present study, in addition to measuring inositol lipid turnover as indicated by inositol monophosphate (IP) accumulation, we have also monitored the effect of oestradiol on the incorporation of both 3H-inositol and 14C-glycerol into MCF-7 cell phospholipids. Pre-treatment of MCF-7 cells with oestradiol (10 nM) for 48 hr stimulated a 4.3-fold increase in IP production. This was similarly accompanied by a 3.4-fold increase in the incorporation of 3H-inositol into total phosphoinositides and a 40% increase in cell growth. The oestrogen antagonist LYI 17018 completely attenuated these effects. Oestradiol also stimulated 14C-glycerol incorporation into phosphatidyl inositol, -choline and -ethanolamine by 97%, 82% and 99%, respectively. IP production in response to bombesin was potentiated by oestradiol in a dose-dependent fashion. Fluoroaluminate (AlF4-) stimulated a dose-dependent increase in IP production and oestradiol pre-treatment increased the sensitivity of this IP response to AlF4-. Medroxyprogesterone acetate inhibited bombesin-stimulated IP production but had no effect on the response to AlF4-. Our data suggest that the oestrogenic action on basal IP production in MCF-7 cells may reflect an effect on inositol lipid synthesis rather than turnover. However, the potentiation by oestradiol of both bombesin- and AlF4(-)-stimulated inositol lipid hydrolysis suggests the operation of a post-receptor regulatory mechanism(s) which is independent of the inositol lipid pool size.
Schrey
M P
MP
Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Furlong
M M
MM
Holt
J R
JR
Patel
K V
KV
D000535:Aluminum / Q000494:pharmacology*; D001839:Bombesin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005461:Fluorine / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D050356:Lipid Metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; C053629:fluoroaluminum; D005461:Fluorine; D007294:Inositol; D004958:Estradiol; D000535:Aluminum; D001839:Bombesin