Abstract
Abstract Our lab has identified soluble guanylyl cyclase α1 (sGCα1) as a novel androgen- regulated gene involved in prostate cancer cell proliferation. A well-known biological function of sGCα1 is to heterodimerize with sGCβ1 forming the enzyme sGC, which mediates nitric oxide(NO) signaling. Our published data demonstrated that the sGCα1 effect on prostate cancer cell growth is independent of the classical mediators of NO signaling, suggesting that sGCα1 acts via a novel signaling pathway. Furthermore, sGCα1 expression is highly elevated in prostate tumors and this expression is directly correlated to the progression stage of prostate cancer. Interestingly, we have recently discovered that sGCα1 can inhibit the transcriptional activity of p53 via a mechanism that does not depend on classical mediators of NO signaling. Immunoprecipitation and immunocytochemistry assays have shown an association between sGCα1 and p53 and these data suggest that sGCa1 inhibits p53 by mediating the cytoplasmic sequestration of this tumor suppressor protein, which would represent a previously unknown mechanism for p53 regulation. sGCa1 can also regulate in a gene-specific manner p53-regulated gene expression, targeting genes involved in apoptosis. In addition, sGCa1 makes prostate cancer cells resistant to the chemotherapeutic and apoptosis-inducing drug Etoposide. Finally, analysis of prostate tumors has shown a direct correlation in expression between sGCα1 and p53. Collectively, these data suggest that sGCa1 regulation of p53 activity is important in prostate cancer biology and may represent an import mechanism of p53 down-regulation in those prostate cancers that express significant levels of p53. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 215. doi:10.1158/1538-7445.AM2011-215
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