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

Publication ,  Journal Article
Chen, R; Zeng, X; Zhang, R; Huang, J; Kuang, X; Yang, J; Liu, J; Tawfik, O; Thrasher, JB; Li, B
Published in: Urol Oncol
July 2014

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.

Duke Scholars

Published In

Urol Oncol

DOI

EISSN

1873-2496

Publication Date

July 2014

Volume

32

Issue

5

Start / End Page

524 / 536

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transcriptional Activation
  • Signal Transduction
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Male
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

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Chen, R., Zeng, X., Zhang, R., Huang, J., Kuang, X., Yang, J., … Li, B. (2014). Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol Oncol, 32(5), 524–536. https://doi.org/10.1016/j.urolonc.2013.05.011
Chen, Ruibao, Xing Zeng, Ruitao Zhang, Jiaoti Huang, Xiangxing Kuang, Jun Yang, Jihong Liu, Ossama Tawfik, James Brantley Thrasher, and Benyi Li. “Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers.Urol Oncol 32, no. 5 (July 2014): 524–36. https://doi.org/10.1016/j.urolonc.2013.05.011.
Chen R, Zeng X, Zhang R, Huang J, Kuang X, Yang J, et al. Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol Oncol. 2014 Jul;32(5):524–36.
Chen, Ruibao, et al. “Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers.Urol Oncol, vol. 32, no. 5, July 2014, pp. 524–36. Pubmed, doi:10.1016/j.urolonc.2013.05.011.
Chen R, Zeng X, Zhang R, Huang J, Kuang X, Yang J, Liu J, Tawfik O, Thrasher JB, Li B. Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol Oncol. 2014 Jul;32(5):524–536.
Journal cover image

Published In

Urol Oncol

DOI

EISSN

1873-2496

Publication Date

July 2014

Volume

32

Issue

5

Start / End Page

524 / 536

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transcriptional Activation
  • Signal Transduction
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Male
  • Humans
  • Gene Expression Regulation, Neoplastic