{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:07:34Z","timestamp":1782212854413,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,8,3]],"date-time":"2009-08-03T00:00:00Z","timestamp":1249257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The androgen\u2010signaling 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\u2010deprived conditions, the AR may be activated inappropriately through interaction with other molecules, including cyclic AMP\u2010dependent 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 (RI\u03b1) with small interference RNAs significantly increased the growth\u2010inhibitory and proapoptotic effects of AR knockdown. This treatment strategy was effective in androgen\u2010sensitive and in androgen ablation\u2010resistant prostate cancer cells. In addition, we report that downregulating PKA RI\u03b1 was sufficient to inhibit PKA signaling and interestingly also impaired AR expression and activation. Vice versa, AR knockdown induced a decline in PKA RI\u03b1, associated with reduced PKA activity. This mutual influence on expression level was specific, because siRNAs against the AR did not affect expression of PKA RI\u03b1 in AR negative DU\u2010145 cells and a siRNA control did not affect protein expression. Another important finding of our study was that depletion of PKA RI\u03b1 also potentiated the antiproliferative effect of the antiandrogen bicalutamide in androgen\u2010sensitive LNCaP. We therefore concluded that combined inhibition of PKA RI\u03b1 and AR may be a promising new therapeutic option for prostate cancer patients and might be superior to solely preventing AR expression.<\/jats:p>","DOI":"10.1002\/ijc.24806","type":"journal-article","created":{"date-parts":[[2009,8,3]],"date-time":"2009-08-03T18:51:32Z","timestamp":1249325492000},"page":"775-789","source":"Crossref","is-referenced-by-count":19,"title":["Enhanced antiproliferative and proapoptotic effects on prostate cancer cells by simultaneously inhibiting androgen receptor and cAMP\u2010dependent protein kinase A"],"prefix":"10.1002","volume":"126","author":[{"given":"Andreas","family":"Desiniotis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Klocker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris E.","family":"Eder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,9,16]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1","article-title":"Androgen receptor gene and hormonal therapy failure of prostate cancer","volume":"152","author":"Koivisto P","year":"1998","journal-title":"Am J Pathol"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35094009"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.4065\/82.2.243"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566523052997424"},{"key":"e_1_2_6_6_2","first-page":"385","article-title":"Androgen receptor activity at the prostate specific antigen locus: steroidal and non\u2010steroidal mechanisms","volume":"1","author":"Jia L","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(02)01593-5"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015531326689"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0495-401"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2006.09.008"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.12.1541"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(199606)28:6<392::AID-PROS9>3.0.CO;2-C"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00185971"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(19980401)35:1<63::AID-PROS9>3.0.CO;2-I"},{"key":"e_1_2_6_15_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1210\/mend.15.1.0581","article-title":"Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function","volume":"15","author":"Buchanan G","year":"2001","journal-title":"Mol Endocrinol"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1146-03"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.33.19900"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5026"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0060487"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.12.7777"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1359.014"},{"key":"e_1_2_6_22_2","first-page":"607","article-title":"Protein kinase A RI\u03b1 antisense inhibition of PC3M prostate cancer cell growth: Bcl\u20102 hyperphosphorylation. 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