Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

Chun Liang Chen, Ling Cen, Jennifer Kohout, Brian Hutzen, Christina Chan, Fu Chuan Hsieh, Abbey Loy, Victor Huang, Gong Cheng, Jiayuh Lin

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Background: Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results: We found that elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F) and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC). The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin) and a cell cycle regulating gene (cyclin D1) was associated with the cell growth inhibition and apoptosis. Conclusion: These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

Original languageEnglish (US)
Article number78
JournalMolecular Cancer
Volume7
DOIs
StatePublished - Oct 21 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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