title: The expression and role of tyrosine kinase ETK/BMX in renal cell carcinoma.
abstract: BACKGROUND
  Expression 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.
  
  
  METHODS
  ETK 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.
  
  
  RESULTS
  Immunohistochemistry 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.
  
  
  CONCLUSIONS
  Our 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.
authors.forename: Jintao
authors.initials: J
authors.lastname: Zhuang
authors.forename: Xiangan
authors.initials: X
authors.lastname: Tu
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Cao
authors.forename: Shengjie
authors.initials: S
authors.lastname: Guo
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Mao
authors.forename: Jincheng
authors.initials: J
authors.lastname: Pan
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. qiushp@mail.sysu.edu.cn.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000401:mortality; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C492367:BMX protein, human; D011505:Protein-Tyrosine Kinases