Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J Biol Chem 2003 Jul 18;278(29):27287-92
Date
04/30/2003Pubmed ID
12719422DOI
10.1074/jbc.M304307200Scopus ID
2-s2.0-0038711502 (requires institutional sign-in at Scopus site) 114 CitationsAbstract
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 MTMESH terms used to index this publication - Major topics in bold
AdenoviridaeApoptosis
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