c-fos promoter insensitivity to phorbol ester and possible role of protein kinase C in androgen-independent cancer cells.
In exploring the biological basis of androgen-independent prostate cancer, we observed serum-independent growth of androgen-independent cells. We then discovered that in androgen-independent but not androgen-dependent cells, the serum-responsive gene c-fos is insensitive to phorbol esters, which regulate c-fos through the same mechanisms as serum. Transient expression of protein kinase C, through which phorbol esters activate c-fos, was sufficient to desensitize c-fos in androgen-dependent cells. Incubation in protein kinase C inhibitor chelerythrine killed androgen-independent but not androgen-dependent cells. This finding implicates protein kinase C activity in androgen-independent prostate cancer and suggests novel therapeutic strategies.
Department of Urology, University of Miami School of Medicine, FL 33101.
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Krongrad
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Bai
D000728:Androgens / Q000494:pharmacology*; D016762:Genes, fos; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000728:Androgens; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate