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Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation
Author(s) -
Yu Yue,
Yang Ou,
Fazli Ladan,
Rennie Paul S.,
Gleave Martin E.,
Dong Xuesen
Publication year - 2015
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22988
Subject(s) - stromal cell , prostate cancer , vimentin , prostate , androgen receptor , stroma , cancer research , biology , tissue microarray , immunohistochemistry , medicine , endocrinology , pathology , cancer
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. CONCLUSION These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression. Prostate 75:1043–1050, 2015 . © 2015 Wiley Periodicals, Inc.