The role of phosphatidylinositol 3-kinase in the regulation of cell response to steroid hormones

Phosphatidylinositol 3-kinase (PI-3 kinase) has been implicated in the regulation of many cellular processes, including growth and transformation. We describe the effect of glucocorticoids on cell growth, phosphoinositide formation and PI-3 kinase activity in Rous sarcoma virus-transformed hamster f...

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Bibliographic Details
Published in:Biochimica et biophysica acta 1999-07, Vol.1450 (3), p.434-443
Main Authors: Krasil’nikov, M.A., Shatskaya, V.A., Stavrovskaya, A.A., Erohina, M., Gershtein, E.S., Adler, V.V.
Format: Article
Language:English
Subjects:
Animals
Cell Division - drug effects
Cell Line, Transformed
Cell Survival
Cricetinae
Dexamethasone - pharmacology
Doxorubicin - pharmacology
Drug Resistance
Enzyme Activation - drug effects
Glucocorticoids - pharmacology
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Phosphatidylinositols - analysis
Receptors, Glucocorticoid - analysis
Time Factors
Transfection
Vinblastine - pharmacology
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Summary:Phosphatidylinositol 3-kinase (PI-3 kinase) has been implicated in the regulation of many cellular processes, including growth and transformation. We describe the effect of glucocorticoids on cell growth, phosphoinositide formation and PI-3 kinase activity in Rous sarcoma virus-transformed hamster fibroblasts (HET-SR). Using a prolonged dexamethasone treatment of HET-SR cells we have selected a new glucocorticoid receptor-positive cell subline, HET-SR(h), that was resistant to growth inhibitory action of dexamethasone and/or non-hormonal drugs (vinblastine, adriamycin) and was characterized by higher levels of phosphoinositide formation and increased PI-3 kinase activity. Study of the short-term hormone action has shown that both dexamethasone-sensitive and -resistant sublines responded to hormone by a decrease in phospholipid turnover rate. At the same time, in both cell lines activation of PI-3 kinase after dexamethasone addition was revealed. Dexamethasone-dependent activation of PI-3 kinase was more significant and maintained for a longer period in HET-SR(h) cells than in parent HET-SR cells. Finally, by transfecting p110*, a constitutively active catalytic subunit of PI-3 kinase, into hormone-sensitive HET-SR cells, we have found a marked increase in cell resistance to growth inhibitory dexamethasone action. These results suggest that PI-3 kinase may serve as one of the factors providing cell resistance to cytostatic drugs.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/S0167-4889(99)00066-X