{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(9)"],"submitter":["Maranto C"],"pubmed_abstract":["Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of <i>AR</i> gene transcription. Stat5 suppression inhibited <i>AR</i> gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, and truncated AR proteins. Pharmacological Stat5 inhibition by a specific small-molecule Stat5 inhibitor down-regulated Stat5-inducible genes as well as AR and AR-regulated genes and suppressed PC growth. This work introduces the concept of Stat5 as an inducer of <i>AR</i> gene transcription in PC. Pharmacological Stat5 inhibitors may represent a new strategy for suppressing AR and CRPC growth."],"journal":["Science advances"],"pagination":["eadi2742"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10901378"],"repository":["biostudies-literature"],"pubmed_title":["Stat5 induces androgen receptor (<i>AR</i>) gene transcription in prostate cancer and offers a druggable pathway to target AR signaling."],"pmcid":["PMC10901378"],"pubmed_authors":["Udhane V","McCluskey B","Johnson S","Qi S","Banerjee A","Sabharwal L","Wang L","Maranto C","Pitzen SP","Iczkowski KA","Nevalainen MT","Devi S","Dehm SM","O'Connor C","Jacobsohn K"],"additional_accession":[]},"is_claimable":false,"name":"Stat5 induces androgen receptor (<i>AR</i>) gene transcription in prostate cancer and offers a druggable pathway to target AR signaling.","description":"Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of <i>AR</i> gene transcription. Stat5 suppression inhibited <i>AR</i> gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, and truncated AR proteins. Pharmacological Stat5 inhibition by a specific small-molecule Stat5 inhibitor down-regulated Stat5-inducible genes as well as AR and AR-regulated genes and suppressed PC growth. This work introduces the concept of Stat5 as an inducer of <i>AR</i> gene transcription in PC. Pharmacological Stat5 inhibitors may represent a new strategy for suppressing AR and CRPC growth.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-22T06:39:45.073Z","creation":"2025-04-05T21:49:03.065Z"},"accession":"S-EPMC10901378","cross_references":{"pubmed":["38416822"],"doi":["10.1126/sciadv.adi2742"]}}