{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:28:13Z","timestamp":1762100893171,"version":"3.41.2"},"reference-count":76,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,12,29]],"date-time":"2008-12-29T00:00:00Z","timestamp":1230508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2009,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent reports have shown that the AR is the key determinant of the molecular changes required for driving prostate cancer cells from an androgen\u2010dependent to an androgen\u2010independent or androgen depletion\u2010independent (ADI) state. Several recent publications suggest that down\u2010regulation of AR expression should therefore be considered the principal strategy for the treatment of ADI prostate cancer. However, no valid data is available about how androgen\u2010dependent prostate cancer cells respond to apoptosis\u2010inducing drugs after knocking down AR expression and whether prostate cancer cells escape apoptosis after inhibition of AR expression. This review will focus on mechanisms of prostate cancer cell survival after inhibition of AR activity mediated either by androgen depletion or by targeting the expression of AR by siRNA. We have shown that knocking down AR expression by siRNA induced PI3K\u2010independent activation of Akt, which was mediated by calcium\/calmodulin\u2010dependent kinase II (CaMKII). We also showed that the expression of <jats:italic>CaMKII<\/jats:italic> genes is under AR control: active AR in the presence of androgens inhibits <jats:italic>CaMKII<\/jats:italic> gene expression whereas inhibition of AR activity results in an elevated level of kinase activity and in enhanced expression of <jats:italic>CaMKII<\/jats:italic> genes. This in turn activates the anti\u2010apoptotic PI3K\/Akt pathways. CaMKII also express anti\u2010apoptotic activity that is independent from the Akt pathway. This may therefore be an important mechanism by which prostate cancer cells escape apoptosis after androgen depletion or knocking down AR expression. In addition, we have found that there is another way to escape cell death after AR inhibition: DNA damaging agents cannot fully activate p53 in the absence of AR and as a result p53 down stream targets, for example, microRNA\u201034, cannot be activated and induce apoptosis. This implies that there may be a need for re\u2010evaluation of the therapeutic approaches to human prostate cancer. J. Cell. Biochem. 106: 363\u2013371, 2009. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22022","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T13:36:01Z","timestamp":1230730561000},"page":"363-371","source":"Crossref","is-referenced-by-count":45,"title":["Mechanisms of prostate cancer cell survival after inhibition of AR expression"],"prefix":"10.1002","volume":"106","author":[{"given":"Michael B.","family":"Cohen","sequence":"first","affiliation":[]},{"given":"Oskar 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