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

• Published in: Journal of andrology Vol. 22; no. 3; pp. 471 - 480
• Main Authors: Yang, G, Gregory, C. W, Shang, Q, O'Brien, D. A, Zhang, Y. L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Am Soc Andrology 01.05.2001; Blackwell Publishing Ltd; American Society of Andrology
• Subjects: Androgens - physiology; Animals; Biological and medical sciences; CCAAT-Enhancer-Binding Protein-delta; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; Epididymis - metabolism; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Neoplasm Transplantation; Prostatic Neoplasms - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Testis - metabolism; testosterone; Transcription factor; Transcription Factors; Transplantation, Heterologous; Tumors; Human; Urinary system disease; Androgen; Prostate disease; Rat; Rodentia; Malignant tumor; Gene expression; Binding protein; Testosterone; Vertebrata; Mammalia; Animal; Testicular hormone; Sex steroid hormone; Transcription factor; Male genital diseases; Prostate; Transcription factor C/EBP
• ISSN: 0196-3635; 1939-4640
• DOI: 10.1002/j.1939-4640.2001.tb02204.x

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.