Effect of androgens and their manipulation on cell growth and androgen receptor (AR) levels in AR-positive and -negative human hepatocellular carcinomas

Background/Aims: Little is known about genuine roles of androgens and their receptor in hepatocellular carcinoma. Methods: In the present study, two sublines derived from a human hepatocellular carcinoma cell line KYN-1 were used: KYN-1/SM10 with androgen receptor and KYN-1/SM2 without androgen receptor. Results: The binding assay with 3H-R1881 identified the presence of both cytosolic and nucleosolic androgen receptors in KYN-1/SM10 but not in KYN-1/SM2. In serum-free medium, dihydrotestosterone was able to enhance the cell proliferation and 3H-thymidine incorporation in androgen receptor positive KYN-1/SM10 cells. Such effects of dihydrotestosterone were partially inhibited by an antiandrogen cyproterone acetate in a concentration-dependent manner. On the other hand, the growth of androgen receptor negative KYN-1/SM2 cells was not influenced by dihydrotestosterone and cyproterone acetate at all. When dihydrotestosterone was removed from the medium of KYN-1/SM10 cultures, the nucleosolic androgen receptor decreased to undetectable levels within 8 h and the cytosolic androgen receptor within 48 h. Addition of dihydrotestosterone (10 mM) to the cells that had been deprived of dihydrotestosterone for 24 h partially restored both cytosolic and nucleosolic androgen receptor within 12 h. Conclusion: The current results seem to indicate that the growth of andorgen receptor positive human hepatocellular carcinoma may be enhanced with androgen through androgen receptors and that antiandrogen therapy with cyproterone acetate may be effective in the treatment of androgen receptor-positive hepatocellular carcinoma.