Androgen regulation of soluble guanylyl cyclaseα1 mediates prostate cancer cell proliferation

C. Cai, S. Y. Chen, Z. Zheng, J. Omwancha, M. F. Lin, S. P. Balk, L. Shemshedini

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The growth and progression of prostate cancer are dependent on androgens and androgen receptor (AR), which act by modulating gene expression. Utilizing a gene microarray approach, we have identified the α1-subunit gene of soluble guanylyl cyclase (sGC) as a novel androgen-regulated gene. A heterodimeric cytoplasmic protein composed of one α and one β subunit, sGC mediates the widespread cellular effects of nitric oxide (NO). We report here that, in prostate cancer cells, androgens stimulate the expression of sGCα1. A cloned human sGCα1 promoter is activated by androgen in an AR-dependent manner, suggesting that sGCα1 may be a direct AR target gene. Disruption of sGCα1 expression severely compromises the growth of both androgen-dependent and androgen-independent AR-positive prostate cancer cells. Overexpression of sGCα1 alone is sufficient for stimulating prostate cancer cell proliferation. Interestingly, the major growth effect of sGCα1 is independent of NO and cyclic guanosine monophosphate, a major mediator of the sGC enzyme. These data strongly suggest that sGCα1 acts in prostate cancer via a novel pathway that does not depend on sGCβ1. Tissue studies show that sGCα1 expression is significantly elevated in advanced prostate cancer. Thus, sGCα1 may be an important mediator of the procarcinogenic effects of androgens.

Original languageEnglish (US)
Pages (from-to)1606-1615
Number of pages10
JournalOncogene
Volume26
Issue number11
DOIs
StatePublished - Mar 8 2007

Keywords

  • Androgen receptor
  • Proliferation
  • Prostate cancer
  • Soluble guanylyl cyclase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Cai, C., Chen, S. Y., Zheng, Z., Omwancha, J., Lin, M. F., Balk, S. P., & Shemshedini, L. (2007). Androgen regulation of soluble guanylyl cyclaseα1 mediates prostate cancer cell proliferation. Oncogene, 26(11), 1606-1615. https://doi.org/10.1038/sj.onc.1209956