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Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J Biol Chem 2003 Jul 18;278(29):27287-92

Date

04/30/2003

Pubmed ID

12719422

DOI

10.1074/jbc.M304307200

Scopus ID

2-s2.0-0038711502   96 Citations

Abstract

Identifying regulators of prostate cancer cell survival may lead to new therapeutic strategies for prostate cancer. We now report prevalent activation of transcription factor Stat5 in human prostate cancer and provide novel evidence that blocking activation of Stat5 in human prostate cancer cells leads to extensive cell death. Specifically, Stat5 was activated in 65% of human prostate cancer specimens examined based on nuclear location of tyrosine phosphorylated Stat5. Adenoviral gene delivery of a dominant-negative Stat5 mutant (DNStat5), but not wild-type Stat5, induced cell death of both the androgen-independent human prostate cancer cell line CWR22Rv and the androgen-sensitive LnCap cell line. Endogenous Stat5 was active in both CWR22Rv and LnCap cells. In contrast, only low levels of inactive Stat5 proteins were detected in the PC-3 cell line, which correlated with resistance to DNStat5-induced cell death. In CWR22Rv and LnCap cells, inhibition of Stat5 by expression of DNStat5 induced apoptotic cell death as judged from morphological changes, DNA fragmentation, and caspase-3 activation with evidence of a caspase-9-dependent mechanism. We propose that blocking Stat5 function may represent a novel therapeutic approach for prostate cancer.

Author List

Ahonen TJ, Xie J, LeBaron MJ, Zhu J, Nurmi M, Alanen K, Rui H, Nevalainen MT

Authors

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




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

Adenoviridae
Apoptosis
Base Sequence
Caspase 3
Caspases
DNA
DNA Fragmentation
DNA-Binding Proteins
Genetic Therapy
Humans
Male
Milk Proteins
Mutagenesis
Prostatic Neoplasms
STAT5 Transcription Factor
Trans-Activators
Tumor Cells, Cultured
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc