Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial cells.
Various cofactors have been shown to regulate androgen receptor (AR) transactivation, but their physiological functions in the AR pathway and prostate tumorigenesis are undefined. Here, we found that AR cofactor (p44) translocation from the nucleus to the cytoplasm in prostate epithelial cells (ECs) is associated with prostate tumorigenesis. The forced nuclear localization of p44 inhibited prostate cancer cell growth by G1 cell-cycle arrest. Consistently, mice lacking one allele of the p44 gene developed prostatic hyperplasia. Therefore, p44 is required for proper expression of AR-target genes to maintain the differentiation of prostate ECs, and p44 translocation from the nucleus into the cytoplasm in prostate cancer cells or loss of one allele in mouse results in excessive prostate EC proliferation.
Zhou
Liran
L
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard-173, Houston, Texas 77030, USA.
Wu
Hong
H
Lee
Peng
P
Wang
Zhengxin
Z
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D019913:Nuclear Localization Signals / Q000502:physiology; D011467:Prostate / Q000166:cytology / Q000254:growth & development*; D011470:Prostatic Hyperplasia / Q000235:genetics; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D021381:Protein Transport; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D019913:Nuclear Localization Signals; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D014157:Transcription Factors; C478359:WDR77 protein, human