Open AccessElevation of androgen receptor promotes prostate cancer metastasis by induction of epithelial‐mesenchymal transition and reduction of KAT 5
Author(s) -
Lin ChingYu,
Jan YeeJee,
Kuo LiKuo,
Wang BiJuan,
Huo Chieh,
Jiang Shih Sheng,
Chen ShyhChang,
Kuo YingYu,
Chang ChuangRung,
Chuu ChihPin
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13776
Subject(s) - gene knockdown , androgen receptor , prostate cancer , vimentin , cancer research , epithelial–mesenchymal transition , metastasis , prostate , slug , biology , immunohistochemistry , medicine , cancer , cell culture , genetics
Androgen receptor ( AR ), an androgen‐activated transcription factor, belongs to the nuclear receptor superfamily. AR plays an important role in the development and progression of prostate cancer ( PC a). However, the role of AR in PC a metastasis is not fully understood. To investigate the role of AR in PC a metastasis, we examined AR expression level in primary and metastatic PC a by analyzing gene array data of 378 primary prostate tumors and 120 metastatic prostate tumors from Oncomine, as well as carrying out immunohistochemical ( IHC ) staining of 56 prostate cancer samples. Expression of mRNA and protein of AR as well as its target gene prostate‐specific antigen ( PSA ) was much higher in metastatic prostate tumors than in primary prostate tumors. Knockdown of AR with si RNA or treating with anti‐androgen Casodex reduced migration and invasion ability of C4‐2B PC a cells. Knockdown of AR increased protein expression of E‐cadherin and AR coregulator KAT 5 but reduced expression of epithelial‐mesenchymal transition ( EMT ) marker proteins Slug, Snail, MMP ‐2, vimentin, and β‐catenin. Knockdown of KAT 5 increased migration of C4‐2B cells, whereas overexpression of KAT 5 suppressed cell migration. KAT 5 knockdown rescues the suppressive effect of AR knockdown on migration of C4‐2B cells. Gene expression level of AR and KAT 5 showed a negative correlation. PC a patients with higher AR expression or lower KAT 5 expression correlated with shorter recurrence‐free survival. Our study suggested that elevation of AR expression and AR signaling in prostate tumors promotes PC a metastasis by induction of EMT and reduction of KAT 5.