Enhanced EGR1 activity promotes the growth of prostate cancer cells in an androgen-depleted environment.
During anti-hormonal therapy for prostate cancer, a major clinical problem is the development of androgen-independent disease. The molecular mechanisms underlying the transition to androgen independence are the subject of intense investigation. In many prostate tumors, the activity of the transcription factor EGR1 (early growth response gene 1) is elevated due to overexpression of EGR1 and/or downregulation of the co-repressor, NAB2. We have modeled these alterations by expressing active EGR1 that does not bind NAB co-repressor proteins in human prostate carcinoma cells. We show here that active EGR1 expression enhances the androgen-independent growth of prostate carcinoma cells in vitro and in vivo. Employing RNAi and expression analyses, we show that EGR1 mediates its effects, at least in part, through the AR signaling pathway. These findings support a role for enhanced EGR1 activity in regulating the transition from androgen-dependent to androgen-independent prostate cancer.
Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Shan-Zhong
SZ
Yang
Isam A
IA
Eltoum
Sarki A
SA
Abdulkadir
D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D017373:Cyproterone Acetate / Q000378:metabolism / Q000494:pharmacology; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000728:Androgens; D051766:Early Growth Response Protein 1; D017373:Cyproterone Acetate