The expression and role of tyrosine kinase ETK/BMX in renal cell carcinoma.
The expression and role of tyrosine kinase ETK/BMX in renal cell carcinoma.
复制标题
酪氨酸激酶ETK/BMX在肾细胞癌中的表达及作用
DOI：
10.1186/1756-9966-33-25
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发表时间：
2014-03-07
期刊：
影响因子：
--
通讯作者：
Qiu S
中科院分区：
文献类型：
--
作者：
Zhuang J;Tu X;Cao K;Guo S;Mao X;Pan J;Huang B;Chen X;Gao Y;Qiu S
非受体酪氨酸激酶ETK/BMX在几种实体瘤中的表达已有报道，但其在肾细胞癌(RCC)中的表达机制及其临床意义尚不清楚。为进一步阐明ETK在肾癌中的生物学功能，采用Western印迹法检测ETK蛋白在肾癌细胞系中的表达水平。采用四甲基偶氮唑蓝比色法、流式细胞仪和Transwell比色法检测ETK对肾癌细胞生长、凋亡、迁移和侵袭的影响。结果免疫组织化学结果显示，ETK在肾癌组织中的表达明显增强，且与临床分期、分级及转移呈正相关。同时，ETK高表达患者的总体生存时间明显短于ETK低表达患者。肾癌细胞株中也检测到ETK。此外，下调ETK可显著抑制肾癌细胞的生长、迁移、侵袭，促进细胞凋亡。结论ETK的过度表达与肾细胞癌的恶性程度和疾病进展有关。由于ETK还参与肾细胞癌的细胞生物学功能和血管内皮生长因子-ETK-STAT3环，因此ETK可能成为肾癌的潜在治疗靶点。
BackgroundExpression of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors, but the underlying molecular mechanisms and its clinical significance in renal cell carcinoma (RCC) remain to be elucidated.MethodsETK expression in 90 human RCC and 30 human normal renal tissue samples was examined by immunohistochemistry and compared with several clinicopathologic parameters. To further demonstrate the biological function of ETK in RCC, Western blot was used to test the expression level of ETK protein in RCC cell lines. Subsequent to the downregulation of ETK by small interfering RNA, the effects of ETK on RCC cell growth, apoptosis, migration and invasion were assessed by methyl thiazol tetrazolium assay, flow cytometry and transwell assay. And the varying expression of VEGF, STAT3 and phosphorylated STAT3 (p-STAT3) in RCC were evaluated by Western blot.ResultsImmunohistochemistry analysis showed that ETK expression was highly increased in RCC and was positively correlated with clinical stage, grade and metastasis. Simultaneously, the overall survival time in patients with higher ETK expression was obviously shorter than that in patients with lower ETK expression. ETK was also detected in RCC cell lines. Moreover, the down-regulating ETK significantly inhibited RCC cell growth, migration, invasion and promoted apoptosis. The expression of VEGF and p-STAT3 were also decreased.ConclusionsOur study suggests that the overexpression of ETK is associated with the malignancy and disease progression of RCC. Since ETK is also involved in RCC cell biological function and VEGF-ETK-STAT3 loop, ETK may be used as a potential therapeutic target for RCC.
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