title: Increased CK5/CK8-positive intermediate cells with stromal smooth muscle cell atrophy in the mice lacking prostate epithelial androgen receptor.
abstract: Results from tissue recombination experiments documented well that stromal androgen receptor (AR) plays essential roles in prostate development, but epithelial AR has little roles in prostate development. Using cell specific knockout AR strategy, we generated pes-ARKO mouse with knock out of AR only in the prostate epithelial cells and demonstrated that epithelial AR might also play important roles in the development of prostate gland. We found mice lacking the prostate epithelial AR have increased apoptosis in epithelial CK8-positive luminal cells and increased proliferation in epithelial CK5-positive basal cells. The consequences of these two contrasting results could then lead to the expansion of CK5/CK8-positive intermediate cells, accompanied by stromal atrophy and impaired ductal morphogenesis. Molecular mechanism dissection found AR target gene, TGF-β(1), might play important roles in this epithelial AR-to-stromal morphogenesis modulation. Collectively, these results provided novel information relevant to epithelial AR functions in epithelial-stromal interactions during the development of normal prostate, and suggested AR could also function as suppressor in selective cells within prostate.
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China. niuyuanjie@gmail.com
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Shang
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
authors.forename: Chih-Rong
authors.initials: CR
authors.lastname: Shyr
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D055786:Gene Knockout Techniques; D006801:Humans; D053555:Keratin-5 / Q000378:metabolism*; D053533:Keratin-8 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D011467:Prostate / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000172:deficiency* / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053555:Keratin-5; D053533:Keratin-8; D011944:Receptors, Androgen; D053773:Transforming Growth Factor beta1