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Heterologous regulation of inositol lipid hydrolysis in human breast cancer cells by oestradiol 17β, bombesin and fluoroaluminate
Author(s) -
Schrey M. P.,
Furlong M. M.,
Holt J. R.,
Patel K. V.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510118
Subject(s) - inositol , endocrinology , bombesin , medicine , inositol phosphate , chemistry , inositol trisphosphate , phospholipase c , receptor , biology , neuropeptide
Inositol lipid turnover has been implicated in the action of oestradiol 17β 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 3 H‐inositol and 14 C‐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 3 H‐inositol into total phosphoinositides and a 40% increase in cell growth. The oestrogen antagonist LY117018 completely attenuated these effects. Oestradiol also stimulated 14 C‐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 (AIF 4 − ) stimulated a dose‐dependent increase in IP production and oestradiol pre‐treatment increased the sensitivity of this IP response to AIF 4 − . Medroxyprogesterone acetate inhibited bombesin‐stimulated IP production but had no effect on the response to AIF 4 − . 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 AIF 4 − ‐stimulated inositol lipid hydrolysis suggests the operation of a post‐receptor regulatory mechanism(s) which is independent of the inositol lipid pool size.