Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells.
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.
Tan
Shyh-Han
SH
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Dagvadorj
Ayush
A
Shen
Feng
F
Gu
Lei
L
Liao
Zhiyong
Z
Abdulghani
Junaid
J
Zhang
Ying
Y
Gelmann
Edward P
EP
Zellweger
Tobias
T
Culig
Zoran
Z
Visakorpi
Tapio
T
Bubendorf
Lukas
L
Kirken
Robert A
RA
Karras
James
J
Nevalainen
Marja T
MT
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
D000728:Androgens; D011944:Receptors, Androgen; D050799:STAT5 Transcription Factor