Novel ZEB1 expression in bladder tumorigenesis

作者: Patrick A. Kenney , Matthew F. Wszolek , Kimberly M. Rieger-Christ , Brasil Silva Neto , Justin J. Gould

DOI: 10.1111/J.1464-410X.2010.09489.X

关键词:

摘要: What’s known on the subject? and What does study add? Epithelial-mesenchymal transition (EMT) is involved in tumor progression where underlying cellular changes associated with EMT have been identified vitro models confirmed a limited number of vivo studies. ZEB1, which targets E-cadherin repression, transcriptional regulator that has implicated EMT, uterine colorectal cancers. Regulation ZEB1 expression shown to involve different microRNAs (miRNAs), identifying potential role for miRNA EMT. In present we novel bladder tumours enhanced migration invasion assays. Confirmation was tissue microarrays (TMAs). OBJECTIVE To evaluate tumorigenesis define possible this transcription factor urothelial carcinomas (UCBs). MATERIALS METHODS Five hundred fifty-eight samples were assembled 10 (TMAs; 263 non-muscle-invasive Ta/T1/Tis, 295 muscle-invasive T2–T4). All transitional cell (TCCs) processed immunohistochemistry assess nuclear expression. Expression levels modulated carcinoma lines CUBIII or UM-UC-3 after forced shRNA knockdown, respectively. Protein determined using western blot analysis transfectants assessed standard assays. RESULTS Nuclear recorded 22.8% UCBs 21.7% UCBs, including 24.1% grade I/II 21.1% III tumours, absent normal mucosa. No significant correlation observed tumour stage grade, nodal involvement, vascular invasion, metastasis overall cancer-specific survival. The introduction knockdown showed reduced invasive potential, Changes accompanied by altered microRNA (miRNA) events linked epithelial–mesenchymal (EMT). CONCLUSION The results cancer absence link clinical variables change, However, assays reduction respectively, transfected lines. Modulation closely miR-200 family along alternative prognostic indicators progression.

参考文章(38)
Philip A. Gregory, Andrew G. Bert, Emily L. Paterson, Simon C. Barry, Anna Tsykin, Gelareh Farshid, Mathew A. Vadas, Yeesim Khew-Goodall, Gregory J. Goodall, The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 Nature Cell Biology. ,vol. 10, pp. 593- 601 ,(2008) , 10.1038/NCB1722
Manav Korpal, Esther S. Lee, Guohong Hu, Yibin Kang, The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry. ,vol. 283, pp. 14910- 14914 ,(2008) , 10.1074/JBC.C800074200
P J Miettinen, R Ebner, A R Lopez, R Derynck, TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. Journal of Cell Biology. ,vol. 127, pp. 2021- 2036 ,(1994) , 10.1083/JCB.127.6.2021
Meenakshi Singh, Nicole S Spoelstra, Annie Jean, Erin Howe, Kathleen C Torkko, Hilda R Clark, Douglas S Darling, Kenneth R Shroyer, Kathryn B Horwitz, Russell R Broaddus, Jennifer K Richer, ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease Modern Pathology. ,vol. 21, pp. 912- 923 ,(2008) , 10.1038/MODPATHOL.2008.82
Margit A Huber, Norbert Kraut, Hartmut Beug, Molecular requirements for epithelial-mesenchymal transition during tumor progression. Current Opinion in Cell Biology. ,vol. 17, pp. 548- 558 ,(2005) , 10.1016/J.CEB.2005.08.001
Kirsten Aigner, Luise Descovich, Mario Mikula, Aneesa Sultan, Brigitta Dampier, Stefan Bonné, Frans van Roy, Wolfgang Mikulits, Martin Schreiber, Thomas Brabletz, Wolfgang Sommergruber, Norbert Schweifer, Andreas Wernitznig, Hartmut Beug, Roland Foisner, Andreas Eger, The transcription factor ZEB1 (δEF1) represses Plakophilin 3 during human cancer progression FEBS Letters. ,vol. 581, pp. 1617- 1624 ,(2007) , 10.1016/J.FEBSLET.2007.03.026
Ali Nawshad, Damian LaGamba, Ahmad Polad, Elizabeth D. Hay, Transforming Growth Factor-β Signaling during Epithelial-Mesenchymal Transformation: Implications for Embryogenesis and Tumor Metastasis Cells Tissues Organs. ,vol. 179, pp. 11- 23 ,(2005) , 10.1159/000084505
Maria C. Elias, Kathleen R. Tozer, John R. Silber, Svetlana Mikheeva, Mei Deng, Richard S. Morrison, Thomas C. Manning, Daniel L. Silbergeld, Carlotta A. Glackin, Thomas A. Reh, Robert C. Rostomily, TWIST is Expressed in Human Gliomas and Promotes Invasion Neoplasia. ,vol. 7, pp. 824- 837 ,(2005) , 10.1593/NEO.04352
Amparo Cano, M. Angela Nieto, Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends in Cell Biology. ,vol. 18, pp. 357- 359 ,(2008) , 10.1016/J.TCB.2008.05.005