Altered differentiation and proliferation of prostate epithelium in mice lacking the androgen receptor cofactor p44/WDR77.
Although it has been observed that various cofactors modulate activity of the androgen receptor (AR), the specific relationship between AR cofactors and prostate development and functions has not been well studied. To determine whether AR cofactor p44/WDR77 is important in prostate growth and development, we examined prostate architecture in p44/WDR77-null mice and wild-type (WT) littermates. Prostate glands from p44/WDR77-deficient animals were not only smaller than those from WT mice but also had fewer branches and terminal duct tips and were deficient in production of secretory proteins. The p44/WDR77-null prostate tissue was less differentiated and hyperproliferative relative to WT littermates. In addition, the altered expression of androgen-regulated genes was observed in the p44/WDR77-null prostate. Thus, these results suggest that the AR cofactor p44/WDR77 plays important roles in prostate growth and differentiation by modulating AR-target gene expression.
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Shen
S
Gao
Hong
H
Wu
Fen
F
Wang
Zhengxin
Z
Wang
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D011247:Pregnancy; D011467:Prostate / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D011944:Receptors, Androgen; D014157:Transcription Factors; C503486:WDR77 protein, mouse