{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:52:04Z","timestamp":1769615524672,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Prostate cancer (PCa) is a leading malignancy among men, with treatment resistance posing significant clinical challenges, especially in advanced, castration\u2010resistant cases. Abiraterone acetate (AA), a CYP17A1 inhibitor, suppresses androgen biosynthesis and is used to manage metastatic disease; however, its complete mechanism of action is not fully understood. This study investigates whether AA modulates androgen receptor (AR) expression via endoplasmic reticulum (ER) stress in PCa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LNCaP (androgen\u2010sensitive) and 22Rv1 (AR\u2010variant\u2010expressing) PCa cells were treated with AA (0.5\u201316\u2009\u03bcM) for 24\u201372\u2009h. Cytotoxicity and proliferation were assessed via CCK\u20108 and BrdU assays. Apoptosis was quantified by caspase\u20103\/7 activation. ER stress markers (PERK, ATF4, CHOP) and AR were evaluated using RT\u2010qPCR, Western blot, and immunofluorescence staining. Pharmacological PERK inhibition (GSK2656157) and activation (CCT020312) validated pathway involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AA induced concentration\/time\u2010dependent cytotoxicity in LNCaP cells (24\u2009h IC\u2085\u2080\u2009=\u20094.8\u2009\u03bcM) and 22Rv1 cells (24\u2009h IC\u2085\u2080\u2009=\u200915.2\u2009\u03bcM) and proliferation decreased by 54.1% and 7.3% at 4.8\u2009\u03bcM, respectively. AA triggered apoptosis in LNCaP cells, increasing caspase\u20103\/7\u2010positive cells to 71.58% vs. 1.73% in controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Mechanistically, AA upregulated PERK, ATF4, and CHOP mRNA\/protein (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) while downregulating AR. Immunofluorescence confirmed reciprocal ATF4 nuclear accumulation and AR reduction in AA\u2010treated LNCaP cells. PERK inhibition reversed AA\u2010induced effects, while PERK activation phenocopied AA's AR suppression and cytotoxicity, confirming ER stress mediation via the PERK\/ATF4\/CHOP axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AA induces ER stress, leading to transcriptional downregulation of the AR and suppression of PCa cell viability and proliferation. Targeting the PERK pathway may enhance AA efficacy in AR\u2010driven PCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70304","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T04:00:11Z","timestamp":1764820811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Abiraterone Acetate Triggers\n                    <scp>ER<\/scp>\n                    Stress\u2010Mediated Androgen Receptor Suppression via\n                    <scp>PERK<\/scp>\n                    \/\n                    <scp>ATF4<\/scp>\n                    \/\n                    <scp>CHOP<\/scp>\n                    Signaling in Prostate Cancer"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-512X","authenticated-orcid":false,"given":"Ekrem","family":"Basaran","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine D\u00fczce 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