- 作者：Zhi Yu Wang ; M.D.a ; Fu Qing Zeng ; Ph.D.a ; Zhao Hui Zhu ; Ph.D.a ; zhuzhaohui316@sina.com ; Guo Song Jiang ; M.D.a ; Lei Lv ; M.D.a ; Feng Wan ; M.D.a ; Rui Dong ; M.D.a ; Xing Yuan Xiao ; M.D.a ; Shi An Xing ; M.D.b
- 关键词：Thymosin 尾4 ; ILK ; E-cadherin ; 尾-Catenin ; Epithelial-mesenchymal transition ; TCC
- 刊名：Urologic Oncology ; Seminars and Original Investigations
- 出版年：2012
- 期刊代码：266_10781439
- 类别：med
- 出版时间：March-April, 2012
- 卷：30
- 期：2
- 页码：167-176
- 文件大小：2612 K
Objectives
To study the underlying alteration in the expression of epithelial markers involved in epithelial-mesenchymal transition (EMT), and elucidate the potential mechanism(s) for T尾4-induced EMT-like phenotypic changes in bladder cancer cells.Materials and methods
All tissue samples in this study were obtained from clinical patients of the Union Hospital of Tongji Medical College, and were confirmed by surgery and pathology. Of these, normal bladder tissues (control), primary urothelial carcinoma of different grades (Stage pTa, Stage pT3), bladder paracancerous tissues, accompanied with 2 bladder cancer cell lines (BIU-87 and T24), were divided into 6 groups. Quantitative RT-PCR, Western blotting, and immunohistochemical study of adhesion molecules T尾4, ILK, E-cadherin, and 尾-catenin involved in EMT were carried out. A lentiviral gene transferring vector containing the RNA polymerase III-dependent U6 promoter to express short hairpin RNA (shRNA) directed against T尾4 was also applied. In the present study, all agents were evaluated using commercial kits.
Results
A strong correlation between the expression levels of T尾4, ILK, E-cadherin, and 尾-catenin was found in the bladder transitional cell carcinoma (TCC) patients. In the BIU-87 and T24 bladder cancer cells overexpressing T尾4, which were accompanied by a loss of E-cadherin as well as a cytosolic accumulation of 尾-catenin, up-regulation of ILK was also revealed. The inhibition of the T尾4 expression with lentiviral shRNA vector could raise EMT-like phenotypic changes, significantly depressed motility, and subsequent invasiveness of bladder cancer cells.
Conclusions
Our results imply that the T尾4 is likely to play a crucial role in EMT progression, and that inhibition of the T尾4 expression or interactions with other genes should be novel therapeutic targets for bladder cancers with high invasive and metastatic potential.