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Molecular Cancer
Published in: Molecular Cancer 1/2008

Open Access 01-12-2008 | Research

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

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

Published in: Molecular Cancer | Issue 1/2008

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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.
Appendix
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Metadata
Title
Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival
Authors
Chun-Liang Chen
Ling Cen
Jennifer Kohout
Brian Hutzen
Christina Chan
Fu-Chuan Hsieh
Abbey Loy
Victor Huang
Gong Cheng
Jiayuh Lin
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2008
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-7-78

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