Open AccessCLDN 8 , an androgen‐regulated gene, promotes prostate cancer cell proliferation and migration
Author(s) -
Ashikari Daisaku,
Takayama Kenichi,
Obinata Daisuke,
Takahashi Satoru,
Inoue Satoshi
Publication year - 2017
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.13269
Subject(s) - prostate cancer , claudin , androgen receptor , cancer research , gene knockdown , signal transduction , cell growth , biology , cancer , cancer cell , androgen , microbiology and biotechnology , tight junction , endocrinology , gene , genetics , hormone
The proliferation of prostate cancer cells is controlled by the androgen receptor ( AR ) signaling pathway. However, the function of AR target genes has not been fully elucidated. In previous studies, we have identified global AR binding sites and AR target genes in prostate cancer cells. Here, we focused on Claudin 8 ( CLDN 8), a protein constituting tight junctions in cell membranes. We found one AR binding site in the promoter region and two functional androgen‐responsive elements in the sequence. Reporter assay revealed that transcriptional activation of the CLDN 8 promoter by androgen is dependent on these androgen‐responsive elements. Furthermore, CLDN 8 mRNA is induced by androgen time‐dependently and the induction is blocked by AR inhibitor, suggesting that AR is involved in the transcriptional activation. In addition, our functional analyses by overexpression and knockdown of CLDN 8 mRNA indicate that CLDN 8 promotes prostate cancer cell proliferation and migration. Claudin 8 was overexpressed in prostate cancer clinical samples compared to benign tissues. Furthermore, we found that CLDN 8 regulates intracellular signal transduction and stabilizes the cytoskeleton. Taken together, these results indicate that CLDN 8 functions as an AR downstream signal to facilitate the progression of prostate cancer. Claudin 8 may be a novel molecular target for prostate cancer therapy.