Differential expression of CCAAT/enhancer-binding protein-delta (c/EBPdelta) in rat androgen-dependent tissues and human prostate cancer.
CCAAT/enhancer-binding protein delta (C/EBPdelta) is a nuclear transcription factor that regulates cellular growth and differentiation. In this study we demonstrate that C/EBPdelta gene expression is differentially regulated in rat androgen-dependent tissues and human prostate cancer. C/EBPdelta messenger RNA (mRNA) levels were very low in adult rat ventral prostate, epididymis, and testis. In ventral prostate and epididymis, expression of C/EBPdelta 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/EBPdelta 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/EBPdelta mRNA declined in response to castration. Both C/EBPdelta mRNA and protein levels increased following testosterone administration. However, C/EBPdelta mRNA and protein levels were variable in recurrent CWR22 tumors growing in the absence of testicular androgen for approximately 5 months. C/EBPdelta 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/EBPdelta levels in androgen-dependent rat tissues, but induces C/EBPdelta expression in androgen-dependent human prostate cancer. Deregulation of C/EBPdelta occurs when prostate cancer progresses to the androgen-independent state.
Yang
G
G
Department of Pediatrics, University of North Carolina at Chapel Hill, USA.
Gregory
C W
CW
Shang
Q
Q
O'Brien
D A
DA
Zhang
Y L
YL
D000728:Androgens / Q000502:physiology*; D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004822:Epididymis / Q000378:metabolism*; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000378:metabolism*; D014157:Transcription Factors; D014183:Transplantation, Heterologous
D000728:Androgens; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; C497254:Cebpd protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta