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• W2018489035 abstract "Abstract The androgen‐signaling pathway with the androgen receptor (AR) as its key molecule is widely understood to influence prostate tumor growth significantly even after androgen ablation. Under androgen‐deprived conditions, the AR may be activated inappropriately through interaction with other molecules, including cyclic AMP‐dependent protein kinase A (PKA). In a previous study, we have shown that knocking down the AR significantly inhibits prostate tumor growth. In this study, we show that combined inhibition of the AR and the regulatory subunit I alpha of PKA (RIα) with small interference RNAs significantly increased the growth‐inhibitory and proapoptotic effects of AR knockdown. This treatment strategy was effective in androgen‐sensitive and in androgen ablation‐resistant prostate cancer cells. In addition, we report that downregulating PKA RIα was sufficient to inhibit PKA signaling and interestingly also impaired AR expression and activation. Vice versa, AR knockdown induced a decline in PKA RIα, associated with reduced PKA activity. This mutual influence on expression level was specific, because siRNAs against the AR did not affect expression of PKA RIα in AR negative DU‐145 cells and a siRNA control did not affect protein expression. Another important finding of our study was that depletion of PKA RIα also potentiated the antiproliferative effect of the antiandrogen bicalutamide in androgen‐sensitive LNCaP. We therefore concluded that combined inhibition of PKA RIα and AR may be a promising new therapeutic option for prostate cancer patients and might be superior to solely preventing AR expression." @default.
• W2018489035 created "2016-06-24" @default.
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• W2018489035 date "2009-09-16" @default.
• W2018489035 modified "2023-10-18" @default.
• W2018489035 title "Enhanced antiproliferative and proapoptotic effects on prostate cancer cells by simultaneously inhibiting androgen receptor and cAMP-dependent protein kinase A" @default.
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• W2018489035 doi "https://doi.org/10.1002/ijc.24806" @default.
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