Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability

Abstract

BACKGROUND: Androgen receptor (AR) may play a role in prostate cancer progression. Coactivator-associated arginine methyltransferase (CARM1) catalyzes methylation of histone H3 at Arg-17. METHODS: Immunohistochemistry of CARM1 was performed on primary prostate cancer specimens. CARM1 recruitment and histone methylation was analyzed by chromatin immunoprecipitation. The effect of CARM1 overexpression or CARM1 knockdown was assessed on reporter assays, cell proliferation, apoptosis, and endogenous androgen target gene expression. RESULTS: CARM1 expression was increased in the nucleus of castration-resistant, but not androgen-stimulated prostate cancer. Androgen stimulation led to CARM1 recruitment and methylation of histone H3 at androgen responsive enhancers. Overexpression of CARM1 stimulated and CARM1 knockdown inhibited AR reporter activity. CARM1 knockdown inhibited cell proliferation and induced apoptosis. CARM1 knockdown inhibited androgen-dependent prostate specific antigen (PSA) and hK2 mRNA expression. CONCLUSIONS: CARM1 is essential for AR function and may play a role in prostate cancer progression. CARM1 may represent a novel therapeutic target in prostate cancer.