EFFECT OF ANDROGENS AND THEIR MANIPULATION ON CELL-GROWTH AND ANDROGEN RECEPTOR (AR) LEVELS IN AR-POSITIVE AND AR-NEGATIVE HUMAN HEPATOCELLULAR CARCINOMAS

Background/Aims: Little is known about genuine roles of androgens and their receptor in hepatocellular carcinoma. Methods: In the present st udy, two sublines derived from a human hepatocellular carcinoma cell l ine KYN-1 were used: KYN-1/SM10 with androgen receptor and KYN-1/SM2 w ithout androgen receptor, Results: The binding assay with H-3-R1881 id entified the presence of both cytosolic and nucleosolic androgen recep tors in KYN-1/SM10 but not in KYN-1/SM2, In serum-free medium, dihydro testosterone was able to enhance the cell proliferation and H-3-thymid ine incorporation in androgen receptor positive ; KYN-1/SM10 cells, Su ch effects of dihydrotestosterone were partially inhibited by an antia ndrogen cyproterone acetate in a concentration-dependent manner. On th e 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/SM1 0 cultures, the nucleosolic androgen receptor decreased to undetectabl e levels within 8 h and the cytosolic androgen receptor within 48 h. A ddition of dihydrotestosterone (10 nM) to the cells that had been depr ived of dihydrotestosterone for 24 h partially restored both cytosolic and nucleosolic androgen receptor within 12 h. Conclusion: The curren t results seem to indicate that the growth of androgen receptor positi ve human hepatocellular carcinoma may be enhanced with androgen throug h androgen receptors and that antiandrogen therapy with cyproterone ac etate may be effective in the treatment of androgen receptor-positive hepatocellular carcinoma.