title: Expression and function of the progesterone receptor in human prostate stroma provide novel insights to cell proliferation control.
abstract: BACKGROUND
  Like other tissues, the prostate is an admixture of many different cell types that can be segregated into components of the epithelium or stroma. Reciprocal interactions between these 2 types of cells are critical for maintaining prostate homeostasis, whereas aberrant stromal cell proliferation can disrupt this balance and result in diseases such as benign prostatic hyperplasia. Although the androgen and estrogen receptors are relatively well studied for their functions in controlling stromal cell proliferation and differentiation, the role of the progesterone receptor (PR) remains unclear.
  
  
  OBJECTIVE
  The aim of the study was to investigate the expression and function of the PR in the prostate.
  
  
  METHODS
  Human prostate biopsies, renal capsule xenografts, and prostate stromal cells were used. Immunohistochemistry, Western blotting, real-time quantitative PCR, cell proliferation, flow cytometry, and gene microarray analyses were performed.
  
  
  RESULTS
  Two PR isoforms, PRA and PRB, are expressed in prostate stromal fibroblasts and smooth muscle cells, but not in epithelial cells. Both PR isoforms suppress prostate stromal cell proliferation through inhibition of the expression of cyclinA, cyclinB, and cdc25c, thus delaying cell cycling through S and M phases. Gene microarray analyses further demonstrated that PRA and PRB regulated different transcriptomes. However, one of the major gene groups commonly regulated by both PR isoforms was the one associated with regulation of cell proliferation.
  
  
  CONCLUSIONS
  PR plays an inhibitory role in prostate stromal cell proliferation.
authors.affiliation: Vancouver Prostate Center, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6H 3Z6.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.forename: Liangliang
authors.initials: L
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Ralph
authors.initials: R
authors.lastname: Buttyan
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Xuesen
authors.initials: X
authors.lastname: Dong
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D049109:Cell Proliferation; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases