Differential expression of CCAAT/enhancer-binding protein-delta (C/EBP delta) in rat androgen-dependent tissues and human prostate cancer

CCAAT/enhancer-binding protein delta (C/EBP delta) is a nuclear transcripti on factor that regulates cellular growth and differentiation. In this study we demonstrate that C/EBP delta gene expression is differentially regulate d in rat androgen-dependent tissues and human prostate cancer. C/EBP delta messenger RNA (mRNA) levels were very low in adult rat ventral prostate, ep ididymis, and testis. In ventral prostate and epididymis, expression of C/E BP delta mRNA increased more than sixfold when testicular testosterone was eliminated by surgical castration or treatment with ethane-1, 2-dimethanesu lfonate (EDS). Testosterone replacement reduced C/EBP delta mRNA levels to near control values in both tissues. CWR22 is a human prostate cancer xenog raft that mimics biological characteristics of androgen-dependent and andro gen-independent human prostate cancer. In androgen-dependent CWR22 tumors, expression of C/EBP delta mRNA declined in response to castration. Both C/E BP delta mRNA and protein levels increased following testosterone administr ation. However, C/ EBP delta mRNA and protein levels were variable in recur rent CWR22 tumors growing in the absence of testicular androgen for similar to5 months. C/EBP delta expression was also variable in androgen-independe nt human prostate carcinomas (n = 3), although mRNA levels were substantial ly lower than those in androgen-dependent tumors (n = 3). These studies dem onstrate that androgen down-regulates C/EBP delta levels in androgen-depend ent rat tissues, but induces C/EBP delta expression in androgen-dependent h uman prostate cancer. Deregulation of C/EBP delta occurs when prostate canc er progresses to the androgen-independent state.