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Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells. Cancer Res 2008 Jan 01;68(1):236-48

Date

01/04/2008

Pubmed ID

18172316

DOI

10.1158/0008-5472.CAN-07-2972

Scopus ID

2-s2.0-39149111601   80 Citations

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.

Author List

Tan SH, Dagvadorj A, Shen F, Gu L, Liao Z, Abdulghani J, Zhang Y, Gelmann EP, Zellweger T, Culig Z, Visakorpi T, Bubendorf L, Kirken RA, Karras J, Nevalainen MT

Author

Marja T. Nevalainen MD, PhD Assistant Dean, Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Active Transport, Cell Nucleus
Androgens
Cell Nucleus
Gene Expression Regulation, Neoplastic
Humans
Immunoprecipitation
Male
Neoplasms, Hormone-Dependent
Prostatic Neoplasms
Protein Interaction Mapping
Receptors, Androgen
STAT5 Transcription Factor
Signal Transduction
Transcription, Genetic
Tumor Cells, Cultured
jenkins-FCD Prod-405 0f9a74600e4e79798f8fa6f545ea115f3dd948b2