Abstract 207: PTEN contributes to p53 activation during skin transformation

Abstract

Abstract Our previous studies have shown that the tumor suppressor p53 is activated and translocates to the nucleus, as well as, mitochondria during skin carcinogenesis. However, how p53, a short-lived protein is stabilized, and whether it works with other tumor suppressors remains unclear. We hypothesize that PTEN contributes to TPA-induced p53 activation in the early stages of skin carcinogenesis. Following TPA treatment, PTEN expression in the whole cell lysate was reduced; however, nuclear PTEN expression was increased, and the p53-PTEN interaction was detected via immunoprecipitation in murine skin epidermal JB6 P+ cells, an effect accompanied by an increase in the proapoptotic protein and p53 transcriptional target, Bax. In cell transfection experiments, knocking down PTEN expression via siRNA was sufficient to suppress p53 transcriptional activity as evidenced by decreased Bax expression. Similar effects were seen when p53 transcriptional activity was blocked by pifithrin-α, a specific p53 inhibitor that blocks p53 nuclear translocation. In addition, TPA-induced PTEN expression was significantly reduced in cells that were pre-treated with pifithrin-α. Our results indicate that the tumor suppressor, PTEN, promotes p53 activation in the early stages of TPA-mediated skin tumorigenesis to regulate the expression and transcriptional activity of p53. Therefore modulators of the PTEN- p53 complex can be therapeutically useful in the treatment of skin carcinogenesis and early-stage tumor promotion. 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 207. doi:10.1158/1538-7445.AM2011-207