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

Abstract

ABSTRACT: CCAAT/enhancer‐binding protein δ (C/EBPδ) is a nuclear transcription factor that regulates cellular growth and differentiation. In this study we demonstrate that C/EBPδ gene expression is differentially regulated in rat androgen‐dependent tissues and human prostate cancer. C/EBPδ messenger RNA (mRNA) levels were very low in adult rat ventral prostate, epididymis, and testis. In ventral prostate and epididymis, expression of C/EBPδ 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/EBPδ mRNA levels to near control values in both tissues. CWR22 is a human prostate cancer xenograft that mimics biological characteristics of androgen‐dependent and androgen‐independent human prostate cancer. In androgen‐dependent CWR22 tumors, expression of C/EBPδ mRNA declined in response to castration. Both C/EBPδ mRNA and protein levels increased following testosterone administration. However, C/EBPδ mRNA and protein levels were variable in recurrent CWR22 tumors growing in the absence of testicular androgen for ∼5 months. C/EBPδ 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/EBPδ levels in androgen‐dependent rat tissues, but induces C/EBPδ expression in androgen‐dependent human prostate cancer. Deregulation of C/EBPδ occurs when prostate cancer progresses to the androgen‐independent state.