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

Department of Urology, Tongji Hospital, Huanzhong University of Science & Technology, Wuhan, China.
Urologic Oncology (Impact Factor: 2.77). 09/2013; 32(5). DOI: 10.1016/j.urolonc.2013.05.011
Source: PubMed


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.

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Available from: Benyi Li, Aug 12, 2015
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    • "Increasingly it is being realized that ligand independent activation of AR is regulated in CACNA1D overexpressing prostate cancer cells. Mechanistically it was reported that ERG induced expression of CACNA1D promoted entry of calcium ions into cytosol [66]. "
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