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Cell Growth & Differentiation Vol. 10, 447-456, June 1999
© 1999 American Association for Cancer Research

Retinoic Acid Induces Selective Expression of Phosphoinositide 3-Kinase {gamma} in Myelomonocytic U937 Cells

Reinhard Baier, Tzvetanka Bondeva, Reinhard Klinger, Andrey Bondev and Reinhard Wetzker1

Research Unit "Molecular Cell Biology" [R. B., T. B., A. B., R. W.] and Institute for Biochemistry II [R. B., R. K.], Medical Faculty, Friedrich-Schiller-University, D-07747 Jena, Germany

Retinoic acid provokes growth inhibition and differentiation of the human leukemic cell line U937 to macrophage-like cells. We report that treatment of U937 cells with all-trans retinoic acid (ATRA), but not the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, results in an increased gene expression of the phosphoinositide 3-kinase (PI3K) species PI3K{gamma}. PI3K{gamma} expression was transcriptionally elevated, indicating that the PI3K{gamma} gene may be a direct target for ATRA. In contrast to its effect on PI3K{gamma} expression, ATRA did neither affect the levels of the PI3K species ß and {delta} nor the adapter proteins p85 and p101. Enhanced expression by ATRA of PI3K{gamma} correlated with an increase of PI3K lipid kinase activity. Additionally, ATRA induced significant and lasting stimulation of mitogen-activated protein kinase/Erk2 activity. This effect was sensitive to the PI3K inhibitors wortmannin or LY294002 and, therefore, attributed to the up-regulation of PI3K{gamma} expression. Our findings suggest that sustained MAPK activation via PI3K{gamma} precedes ATRA-dependent differentiation or growth inhibition.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.