title: Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts.
abstract: BACKGROUND
  Androgens and the androgen receptor (AR) play important roles in the development of male urogenital organs. We previously found that mice with total AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with loss of differentiation. We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate. However, AR roles of stromal fibroblasts in prostate development remain unclear.
  
  
  METHODS
  To further probe the stromal fibroblast AR roles in prostate development, we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development.
  
  
  RESULTS
  The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation, increased apoptosis, and decreased collagen composition. Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors. To further confirm these in vivo findings, we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells, as well as decrease of some stromal growth factors.
  
  
  CONCLUSIONS
  Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate, but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer.
authors: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors: Shengqiang
authors: S
authors: Yu
authors: Chiuan-Ren
authors: CR
authors: Yeh
authors: Yuanjie
authors: Y
authors: Niu
authors: Hong-Chiang
authors: HC
authors: Chang
authors: Yu-Chieh
authors: YC
authors: Tsai
authors: Harold L
authors: HL
authors: Moses
authors: Chih-Rong
authors: CR
authors: Shyr
authors: Chawnshang
authors: C
authors: Chang
authors: Shuyuan
authors: S
authors: Yeh
mesh_terms: D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D011467:Prostate / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D011944:Receptors, Androgen / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011944:Receptors, Androgen; D013739:Testosterone; D003094:Collagen