title: Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells.
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.
authors.affiliation: Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: You
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.forename: Kazutsugu
authors.initials: K
authors.lastname: Uematsu
authors.forename: Julien
authors.initials: J
authors.lastname: Mazieres
authors.forename: Iwao
authors.initials: I
authors.lastname: Mikami
authors.forename: Noemi
authors.initials: N
authors.lastname: Reguart
authors.forename: Terry W
authors.initials: TW
authors.lastname: Moody
authors.forename: Jan
authors.initials: J
authors.lastname: Kitajewski
authors.forename: Frank
authors.initials: F
authors.lastname: McCormick
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051154:Wnt2 Protein
chemical_list: D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D051154:Wnt2 Protein