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Molecular Cancer

, 7:78

First Online: 21 October 2008Received: 25 September 2007Accepted: 21 October 2008


BackgroundConstitutive 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.

ResultsWe 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.

ConclusionThese 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.

AbbreviationsBdSMCbladder smooth muscle cell

DMSOdimethyl sulfoxide

MTT3-4, 5-dimethyl-2-thiazolyl-2, 5-diphenyl-2H-tetrazolium bromide

PIASprotein inhibitors of activated STATs

SHP1-2SH2-containing tyrosine phosphotases

Stat3signal transducer and activator of transcription 3.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-7-78 contains supplementary material, which is available to authorized users.

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Autor: Chun-Liang Chen - Ling Cen - Jennifer Kohout - Brian Hutzen - Christina Chan - Fu-Chuan Hsieh - Abbey Loy - Victor Huang -


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