Overexpression of the β-catenin binding domain of cadherin selectively kills colorectal cancer cells

作者: Michael Pierce , Chunwei Wang , Mark Stump , Alexander Kamb

DOI: 10.1002/IJC.11372

关键词: Cell adhesion moleculeCadherinBinding domainCateninGene expressionHT29 CellsApoptosisCancer researchProgrammed cell deathBiology

摘要: The β-catenin pathway is involved in growth, differentiation and tumor formation. Suppression of activity by expressed inhibitors can cause growth arrest or apoptosis certain colon carcinoma lines. We compare the effects 2 inhibitors, a VE-cadherin cytoplasmic domain fragment (Cad5CD) truncated, dominant-negative Tcf4 (TcfDN), using microplate assay for cell death microarray gene expression analysis. cell-lethal shows that Cad5CD, when HT29 human cells 3 non-colon lines, selectively kills cells. Cad5CD overexpression inhibits β-catenin/Tcf4 transcriptional activity, as determined results from experiments. Our support view an attractive anti-cancer target, especially if binding site itself be exploited drug development. In addition, therapeutically relevant phenotypes such selectivity may difficult to predict analysis alone. Other more specialized phenotypic tests assays required. © 2003 Wiley-Liss, Inc.

参考文章(46)
William Wheatley, Sanghee Yoo, Michael Pierce, Matthew Rebentisch, Mark Endo, Isaac Peterson, Mark Stump, Ken McCormack, Miguel Garcia-Guzman, Alexander Kamb, Genetic Selection for Modulators of the MAP Kinase and β-Catenin Growth-Control Pathways in Mammalian Cells Biochemical Genetics. ,vol. 40, pp. 359- 378 ,(2002) , 10.1023/A:1020705210855
Osamu Tetsu, Frank McCormick, Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. ,vol. 398, pp. 422- 426 ,(1999) , 10.1038/18884
Ie-Ming Shih, Jian Yu, Tong Chuan He, Bert Vogelstein, Kenneth W Kinzler, None, The β-Catenin Binding Domain of Adenomatous Polyposis Coli Is Sufficient for Tumor Suppression Cancer Research. ,vol. 60, pp. 1671- 1676 ,(2000)
Dan L. Longo, Hsingchi Lin, Carl Y. Sasaki, Patrice J. Morin, Truncation of the Extracellular Region Abrogrates Cell Contact but Retains the Growth-suppressive Activity of E-cadherin Cancer Research. ,vol. 60, pp. 7057- 7065 ,(2000)
Richard H. Kramer, Jeffrey W. Karpen, Spanning binding sites on allosteric proteins with polymer-linked ligand dimers Nature. ,vol. 395, pp. 710- 713 ,(1998) , 10.1038/27227
R.T. Moon, J.D. Brown, R. Bates, M. Brannon, D. Kimelman, XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development Development. ,vol. 126, pp. 3159- 3170 ,(1999)
S Sawada, D R Littman, Identification and characterization of a T-cell-specific enhancer adjacent to the murine CD4 gene. Molecular and Cellular Biology. ,vol. 11, pp. 5506- 5515 ,(1991) , 10.1128/MCB.11.11.5506
P. J. Morin, B. Vogelstein, K. W. Kinzler, APOPTOSIS AND APC IN COLORECTAL TUMORIGENESIS Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 7950- 7954 ,(1996) , 10.1073/PNAS.93.15.7950