title: Nur77 inhibits androgen-induced bladder cancer growth.
abstract: Currently, bladder cancer ranks as the second most common genitourinary malignancy which is exacting significant morbidity and mortality worldwide. Although there are abundant epidemiological and basic studies which strongly suggest the role of androgen hormone in bladder cancer, the underlying mechanism is not fully understood. In the current study, we sought to identify a new competitive inhibitor for androgen receptor in bladder cancer cells. Our results showed that Nur77 hyperexpression inhibits UM-UC-3 cell growth and cell cycle progression while Nur77 knockdown exerts the opposite effect. In our cell culture model, we also demonstrated that Nur77 competitively inhibits androgen-dependent transcription activity and more specifically, Nur77 competes with androgen receptor for binding to src-1, a well-known coactivator for steroids. More importantly, we also showed that a small molecule agonist for Nur77, Cytosporone B, significantly inhibits androgen-dependent bladder cancer cell growth in two different cell lines. These data provide a good proof-of-principle that Nur77 signaling machinery could be a new target for growth control of androgen-dependent bladder cancer cells.
authors.affiliation: Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Jia
authors.forename: Hongbin
authors.initials: H
authors.lastname: Song
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D010648:Phenylacetates / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
chemical_list: D059002:Androgen Receptor Antagonists; D000728:Androgens; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010648:Phenylacetates; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; C531461:cytosporone B; D056920:Nuclear Receptor Coactivator 1