Differential Expression of CCAAT/Enhancer-Binding Protein- (C/EBP ) in Rat Androgen-Dependent Tissues and Human Prostate Cancer

CCAAT/enhancer-binding protein (C/EBP ) is a nuclear transcription factor that regulates cellular growth and differentiation. In this study we demonstrate that C/EBP gene expression is differentially regulated in rat androgen-dependent tissues and human prostate cancer. C/EBP messenger RNA (mRNA) levels were very low in adult rat ventral prostate, epididymis, and testis. In ventral prostate and epididymis, expression of C/EBP mRNA increased more than sixfold when testicular testosterone was eliminated by surgical castration or treatment with ethane-1, 2-dimethanesulfonate (EDS). Testosterone replacement reduced C/EBP mRNA levels to near control values in both tissues. CWR22 is a human prostate cancer xenograft that mimics biological characteristics of androgendependent and androgen-independent human prostate cancer. In androgen-dependent CWR22 tumors, expression of C/EBP mRNA declined in response to castration. Both C/EBP mRNA and protein levels increased following testosterone administration. However, C/ EBP mRNA and protein levels were variable in recurrent CWR22 tumors growing in the absence of testicular androgen for 5 months. C/EBP expression was also variable in androgen-independent human prostate carcinomas (n 3), although mRNA levels were substantially lower than those in androgen-dependent tumors (n 3). These studies demonstrate that androgen down-regulates C/EBP levels in androgen-dependent rat tissues, but induces C/EBP expression in androgen-dependent human prostate cancer. Deregulation of C/EBP occurs when prostate cancer progresses to the androgen-independent state.