Farnesyl diphosphate synthase is abundantly expressed and regulated by androgen in rat prostatic epithelial cells

Farnesyl diphosphate synthase (FPPS) has been identified as an androgen-res ponse gene in the rat ventral prostate using a highly sensitive PCR-based c DNA subtraction technique. FPPS is an essential enzyme that catalyzes the s ynthesis of farnesyl diphosphate (FPP), which is required for cholesterol b iosynthesis as well as protein prenylation. We have characterized the expre ssion of FPPS in the rat prostate in response to androgen manipulation. Nor thern blot analysis showed that castration induced a 10-fold down-regulatio n of FPPS mRNA within 24 h in the ventral prostate and androgen replacement up-regulated FPPS mRNA rapidly in the regressed ventral prostate of a cast rated rat. The expression of FPPS was also regulated by androgen in the lat eral and dorsal prostate, indicating that FPPS is important to androgen act ion in all three lobes of the prostate. Western blot analysis showed that F PPS protein level was also regulated by androgen in the prostate. Northern blot analysis of tissue specificity indicated that FPPS was most abundantly expressed in the ventral prostate of a mature rat and was responsive to an drogen manipulation in the prostate and seminal vesicles, but not in other tissues. In situ hybridization study showed that FPPS mRNA was localized to the prostatic epithelium. Interestingly, the expression of FPPS was elevat ed in Dunning rat prostate tumor cell lines. The above findings suggest tha t FPPS has the potential to play an important role in androgen action and p rostate cancer progression. (C) 2001 Elsevier Science Ltd. All rights reser ved.