c-fos promoter insensitivity to phorbol ester and possible role of protein kinase C in androgen-independent cancer cells
Krongrad, A.; Bai, G.
Cancer Research 54(23): 6073-6077
1994
ISSN/ISBN: 0008-5472 PMID: 7954449 Document Number: 438030
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.