| Literature DB >> 15208662 |
Liang You1, Biao He, Zhidong Xu, Kazutsugu Uematsu, Julien Mazieres, Iwao Mikami, Noemi Reguart, Terry W Moody, Jan Kitajewski, Frank McCormick, David M Jablons.
Abstract
In this report, we have demonstrated that Wnt-2 protein is overexpressed in freshly resected human non-small-cell lung cancer (NSCLC) tissues. We have also developed a monoclonal antibody against the N-terminus of human Wnt-2 protein. This monoclonal antibody induces apoptosis in human NSCLC cell lines that overexpress Wnt-2 protein. Incubation of this antibody with normal human airway cells lacking Wnt-2 expression does not induce apoptosis. Wnt-2 signaling blockade by the anti-Wnt-2 antibody is confirmed by downregulation of cytosolic beta-catenin and reduction in TCF-dependent transcriptional activity (TOPFLASH assay). In addition, Wnt-2-specific small interfering RNA (siRNA) treatment in the NSCLC cell line A549 also downregulated cytosolic beta-catenin and induced apoptosis. Moreover, downregulation of an inhibitor of apoptosis family protein, Survivin, was noticed both in the Wnt-2 antibody- and siRNA-treated NSCLC cells, suggesting that inhibition of Wnt-2-mediated signaling induces apoptosis through inactivating Survinin.Entities:
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Year: 2004 PMID： 15208662 DOI： 10.1038/sj.onc.1207844
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867