Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival.
Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival.
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DOI：
10.1186/1476-4598-7-78
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发表时间：
2008-10-21
期刊：
影响因子：
37.3
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Chen CL;Cen L;Kohout J;Hutzen B;Chan C;Hsieh FC;Loy A;Huang V;Cheng G;Lin J
信号转导子和转录激活子3（Stat 3）信号通路的组成性激活在多种人类癌症中起重要作用。Stat 3的激活依赖于上游激酶在酪氨酸残基705处的磷酸化和二聚化后的核转位。目前尚不清楚致癌性Stat 3信号通路是否参与膀胱癌的发生。我们发现100例膀胱癌组织中有19例（19%）以及膀胱癌细胞系WH、UMUC-3和253 J中Stat 3磷酸化水平升高。为了探索Stat 3激活是否与膀胱癌的细胞生长和存活相关，我们使用腺病毒介导的显性阴性Stat 3（Y 705 F）和小分子化合物STA-21靶向膀胱癌细胞中的Stat 3信号通路。两种药物均能抑制膀胱癌细胞株的生长和诱导凋亡，但对正常膀胱平滑肌细胞（BdSMC）无明显作用。凋亡抑制可能通过凋亡caspase 3、8和9途径介导。抗凋亡基因Bcl-2、Bcl-xL和Survivin以及细胞周期调控基因cyclin D1的表达下调与细胞生长抑制和凋亡有关。这些结果表明，Stat 3的激活对膀胱癌细胞的生长和存活至关重要。因此，干扰Stat 3信号通路成为膀胱癌潜在的治疗方法。
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. 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. 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.
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影响因子：
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