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The tumor suppressor gene\n                    <jats:italic>BRCA1<\/jats:italic>\n                    has multiple functions that include secondary processes cooperating with its main function as a caretaker of genomic integrity.\n                    <jats:italic>BRCA1<\/jats:italic>\n                    is often mutated in breast and ovarian cancer, but\n                    <jats:italic>BRCA1<\/jats:italic>\n                    mutations are also associated with PCa, although they are less frequently observed. Most PCa patients do not, however, carry\n                    <jats:italic>BRCA1<\/jats:italic>\n                    mutations, and interestingly, it has been shown that\n                    <jats:italic>BRCA1<\/jats:italic>\n                    expression is enriched in castration\u2010resistant PCa. In this study we elucidated the prostate tissue\u2010specific role of the BRCA1 protein. Although the regulation of DNA damage response genes has been studied in PCa, comprehensive analyses of\n                    <jats:italic>BRCA1<\/jats:italic>\n                    regulation in the context of androgen signaling are lacking. Our results indicate that\n                    <jats:italic>BRCA1<\/jats:italic>\n                    is dynamically regulated by AR signaling and that activation of AR via its natural ligand, dihydrotestosterone, represses BRCA1 expression. Our analyses both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and of patient samples and mouse xenografts showed that BRCA1 expression was induced and sustained after androgen deprivation. Moreover, we observed that oxidative stress\u2013related pathways were regulated by BRCA1 in PCa cells and that androgen deprivation therapy\u2013induced activation of BRCA1 supported the function of NRF2, the master regulator of antioxidant defense, and a known interactor of BRCA1. Impaired NRF2 activity, in the absence of BRCA1, decreased growth in a 3D environment. Our findings shed light on the functional role of BRCA1 protein in PCa and suggest that\n                    <jats:italic>BRCA1<\/jats:italic>\n                    is regulated by the evolving AR signaling state during PCa progression. Thus, AR\u2010mediated suppression of\n                    <jats:italic>BRCA1<\/jats:italic>\n                    accumulates oncogenic alterations in the early phases of PCa tumor progression and safeguards from excessive reactive oxygen species (ROS) when upregulated during androgen deprivation therapy. \u00a9 2025 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6468","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T07:55:04Z","timestamp":1759737304000},"page":"385-398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Androgen receptor\u2010mediated regulation of\n                    <scp>BRCA1<\/scp>\n                    modulates the antioxidant defense in prostate cancer"],"prefix":"10.1002","volume":"267","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-456X","authenticated-orcid":false,"given":"Saiganesh","family":"Sriraman","sequence":"first","affiliation":[{"name":"Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory University of Turku and Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7111-3297","authenticated-orcid":false,"given":"Verneri","family":"Virtanen","sequence":"additional","affiliation":[{"name":"Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory University of Turku and Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Kukkula","sequence":"additional","affiliation":[{"name":"Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory University of Turku and Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervi","family":"Toriseva","sequence":"additional","affiliation":[{"name":"Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory University of Turku and Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni","family":"Lumiainen","sequence":"additional","affiliation":[{"name":"Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory University of Turku and Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun","family":"West","sequence":"additional","affiliation":[{"name":"Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory University of Turku and Turku University Hospital  Turku Finland"},{"name":"InFLAMES Research Flagship Center University of Turku and \u00c5bo 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