{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:32:07Z","timestamp":1791145927645,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T00:00:00Z","timestamp":1342742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"VA Merit Review Program","award":["04H26-AB"],"award-info":[{"award-number":["04H26-AB"]}]},{"name":"DOD Prostate Cancer Res Program","award":["DAMD W81XWH-10-1-0390"],"award-info":[{"award-number":["DAMD W81XWH-10-1-0390"]}]},{"name":"South Central VA Health Care Network (VISN 16) Research Grant"},{"name":"Helis Foundation"},{"name":"John S. Dunn Gulf Coast Consortium for Chemical Genomics (MA Mancini).","award":["NIH 1F32DK85979"],"award-info":[{"award-number":["NIH 1F32DK85979"]}]},{"name":"Diabetes & Endocrinology Research","award":["P30 DK079638"],"award-info":[{"award-number":["P30 DK079638"]}]},{"name":"Imaging resources were supported by BW O'Malley","award":["SCCPR U54 HD-007495"],"award-info":[{"award-number":["SCCPR U54 HD-007495"]}]},{"name":"MK Estes","award":["P30 DK-56338"],"award-info":[{"award-number":["P30 DK-56338"]}]},{"name":"CK Osborne","award":["P30 CA-125123"],"award-info":[{"award-number":["P30 CA-125123"]}]},{"name":"The Dan L. Duncan Cancer Center of Baylor College of Medicine and","award":["DK-79638"],"award-info":[{"award-number":["DK-79638"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The androgen receptor (AR) AR\u2010V7 splice isoform is a constitutively active outlaw transcription factor. Transition of prostate cancer (PC) to the castration\u2010resistant phenotype correlates with AR\u2010V7 accumulation, suggesting that PC progression in patients refractory to conventional therapy is due to the activity of this AR isoform. The mechanism of AR\u2010V7 constitutive activation is not known.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We analyzed potential signaling pathways associated with AR\u2010V7 constitutive activation in PTEN (\u2212) PC\u20103 and LNCaP cells. We used transient and stable transfection, reporter gene assay, RNAi technology together with a number of kinase inhibitors to determine if AR\u2010V7 activation is linked to a kinase\u2010dependent signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In these cell lines, AR\u2010V7 transcriptional activity was inhibited by LY294002, Wortmanin, and AKT inhibitor II. Analysis of the contributing mechanisms demonstrated the involvement of the Phosphatidylinositol 3\u2010kinase (PI3K)\u2010AKT\u2010FOXO1 signaling pathway, and a significant reduction of AR\u2010V7 constitutive activity under conditions of PTEN reactivation.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Our study identifies a pathway regulating AR\u2010V7 constitutive activity and potential therapeutic targets for the treatment of castration\u2010resistant PC. Prostate 73: 267\u2013277, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.22566","type":"journal-article","created":{"date-parts":[[2012,7,21]],"date-time":"2012-07-21T00:12:29Z","timestamp":1342829549000},"page":"267-277","source":"Crossref","is-referenced-by-count":50,"title":["The activity of the androgen receptor variant AR\u2010V7 is regulated by FOXO1 in a PTEN\u2010PI3K\u2010AKT\u2010dependent way"],"prefix":"10.1002","volume":"73","author":[{"given":"Sanjay N.","family":"Mediwala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam T.","family":"Szafran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Hartig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guru","family":"Sonpavde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa G.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perumal","family":"Thiagarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Marcelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20121"},{"key":"e_1_2_6_3_2","first-page":"1008","article-title":"Disruption of androgen receptor function inhibits proliferation of androgen\u2010refractory prostate cancer cells","volume":"62","author":"Zegarra\u2010Moro OL","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm972"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.06.019"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0594"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2764"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3795"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41824"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012443107"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0728"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003605"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20593"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.33.19900"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108255200"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0285159"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1047"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01045.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.11.3024"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","first-page":"e8179","DOI":"10.1371\/journal.pone.0008179","article-title":"Androgen receptor mutations associated with androgen insensitivity syndrome: A high content analysis approach leading to personalized medicine","volume":"4","author":"Szafran AT","year":"2009","journal-title":"PLoS ONE"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7421"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610447200"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2038"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2008-0147"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.16741"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/325365a0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2930761"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-4-8-1105"},{"key":"e_1_2_6_29_2","doi-asserted-by":"crossref","first-page":"13115","DOI":"10.1016\/S0021-9258(17)36806-0","article-title":"A ligand\u2010dependent bipartite nuclear targeting signal in the human androgen receptor. 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