Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability.
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.
Majumder
Samarpan
S
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Liu
Yuanbo
Y
Ford
O Harris
OH
Mohler
James L
JL
Whang
Young E
YE
D000728:Androgens / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008745:Methylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000728:Androgens; D006657:Histones; D011944:Receptors, Androgen; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1