title: Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells.
abstract: The molecular mechanisms underlying progression of prostate cancer to the hormone-independent state are poorly understood. Signal transducer and activator of transcription 5a and 5b (Stat5a/b) is critical for the viability of human prostate cancer cells. We have previously shown that Stat5a/b is constitutively active in high-grade human prostate cancer, but not in normal prostate epithelium. Furthermore, activation of Stat5a/b in primary human prostate cancer predicted early disease recurrence. We show here that transcription factor Stat5a/b is active in 95% of clinical hormone-refractory human prostate cancers. We show for the first time that Stat5a/b synergizes with androgen receptor (AR) in prostate cancer cells. Specifically, active Stat5a/b increases transcriptional activity of AR, and AR, in turn, increases transcriptional activity of Stat5a/b. Liganded AR and active Stat5a/b physically interact in prostate cancer cells and, importantly, enhance nuclear localization of each other. The work presented here provides the first evidence of synergy between AR and the prolactin signaling protein Stat5a/b in human prostate cancer cells.
authors.affiliation: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Shyh-Han
authors.initials: SH
authors.lastname: Tan
authors.forename: Ayush
authors.initials: A
authors.lastname: Dagvadorj
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Gu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liao
authors.forename: Junaid
authors.initials: J
authors.lastname: Abdulghani
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Edward P
authors.initials: EP
authors.lastname: Gelmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Zellweger
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
authors.forename: Tapio
authors.initials: T
authors.lastname: Visakorpi
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kirken
authors.forename: James
authors.initials: J
authors.lastname: Karras
authors.forename: Marja T
authors.initials: MT
authors.lastname: Nevalainen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000728:Androgens / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D050799:STAT5 Transcription Factor