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c-fos Promoter Insensitivity to Phorbol Ester and Possible Role of Protein Kinase C in Androgen-independent Cancer Cells¹

Departments of Urology [A. K., G. B.], Medicine [A. K.], and Biochemistry and Molecular Biology [G. B.], the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, and the Geriatric Research, Education, and Clinical Center, VA Medical Center [A. K., G. B.], Miami, Florida 33101

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.

¹ This work was supported by a Young Investigator Grant from the National Kidney Foundation (A. K.), American Cancer Society Institutional Awards (A. K., G. B.), the Sylvester Comprehensive Cancer Center, and the Geriatric Research, Education, and Clinical Center.

² To whom requests for reprints should be addressed, at Department of Urology, University of Miami School of Medicine, P.O. Box 016960 (M814), Miami, FL 33101.

Received 9/19/94. Accepted 10/28/94.

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