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Altered prostate epithelial development and IGF‐1 signal in mice lacking the androgen receptor in stromal smooth muscle cells
Author(s) -
Yu Shengqiang,
Zhang Caixia,
Lin ChiuChun,
Niu Yuanjie,
Lai KuoPao,
Chang Hongchiang,
Yeh ShauhDer,
Chang Chawnshang,
Yeh Shuyuan
Publication year - 2011
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.21264
Subject(s) - stromal cell , androgen receptor , prostate , mesenchyme , gene knockdown , endocrinology , biology , medicine , prostate cancer , cell growth , stroma , androgen , cancer research , microbiology and biotechnology , apoptosis , chemistry , mesenchymal stem cell , immunohistochemistry , cancer , hormone , biochemistry
BACKGROUND Androgens and the androgen receptor (AR) play critical roles in the prostate development via mesenchymal–epithelial interactions. Smooth muscle cells (SMC), differentiated from mesenchyme, are one of the basic components of the prostate stroma. However, the roles of smooth muscle AR in prostate development are still obscure. METHODS We established the smooth muscle selective AR knockout (SM‐ARKO) mouse model using the Cre‐loxP system, and confirmed the ARKO efficiency at RNA, DNA and protein levels. Then, we observed the prostate morphology changes, and determined the epithelial proliferation, apoptosis, and differentiation. We also knocked down the AR in a prostate smooth muscle cell line (PS‐1) to confirm the in vivo findings and to probe the mechanism. RESULTS The AR was selectively and efficiently knocked out in the anterior prostates of SM‐ARKO mouse. The SM‐ARKO prostates have defects with loss of infolding structures, and decrease of epithelial proliferation, but with little change of apoptosis and differentiation. The mechanism studies showed that IGF‐1 expression level decreased in the SM‐ARKO prostates and AR‐knockdown PS‐1 cells. The decreased IGF‐1 expression might contribute to the defective development of SM‐ARKO prostates. CONCLUSIONS The AR in SMCs plays important roles in the prostate development via the regulation of IGF‐1 signal. Prostate 77:517–524, 2011. © 2010 Wiley‐Liss, Inc.