title: Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation.
abstract: BACKGROUND
  The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated.
  
  
  METHODS
  Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells.
  
  
  RESULTS
  PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently.
  
  
  CONCLUSIONS
  These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression.
authors.affiliation: Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.|The First Hospital, Jilin University, Jilin Province, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Yang
authors.affiliation: Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.affiliation: Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Rennie
authors.affiliation: Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: Department of Urologic Sciences, The Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.|Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Dong
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D017154:Stromal Cells / Q000473:pathology*; D014746:Vimentin / Q000032:analysis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D002135:Calcium-Binding Proteins; D011980:Receptors, Progesterone; D014746:Vimentin
keywords: progesterone receptor; prostate cancer; stromal cell differentiation