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Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers Journal Article


Authors: Chen, Ruibao; Zeng, Xing; Zhang, Ruitao; Huang, Jiaoti; Kuang, Xiangxing; Yang, Jun; Liu, Jihong; Tawfik, Ossama; Thrasher, James Brantley; Li, Benyi
Article Title: Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers
Abstract: Widespread use of L-type calcium channel blockers for treating hypertension has led to multiple epidemiologic studies to assess the risk of prostate cancer incidence. These studies revealed a reverse correlation between the likelihood of prostate cancer risk and the use of L-type calcium channel blockers among men without family history but the mechanism was not clear. In this study, we examined the expression profiles of multiple L-type calcium channel genes in prostate cancers and determined their functional roles in androgen receptor (AR) transactivation and cell growth. By reanalyzing the ONCOMINE database, we found that L-type calcium channel CACNA1D gene expression levels in cancer tissues were significantly higher than noncancer tissues in 14 of 15 published complementary deoxyribonucleic acid microarray data sets, of which 9 data sets showed an increase of 2- to 17-folds. Quantitative polymerase chain reaction and immunostaining experiments revealed that CACNA1D gene and its coding protein α1D were highly expressed in prostate cancers, especially in castration-resistant diseases, compared with benign prostate tissues. Consistent with the notion of CACNA1D as an ERG-regulated gene, CACNA1D gene expression levels were significantly higher in prostate cancers with TMPRSS2-ERG gene fusion compared with the cases without this gene fusion. Blocking L-type channel's function or knocking down CACNA1D gene expression significantly suppressed androgen-stimulated Ca(2+) influx, AR transactivation, and cell growth in prostate cancer cells. Taken together, these data suggest that CACNA1D gene overexpression is associated with prostate cancer progression and might play an important role in Ca(2+) influx, AR activation, and cell growth in prostate cancer cells.
Journal Title: Urologic oncology
Volume: 32
Issue: 5
ISSN: 1873-2496
Publisher: Elsevier  
Date Published: 2014
Start Page: 524
End Page: 536
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