Details

Autor(en) / Beteiligte

• LIANG YOU
• BIAO HE
• JABLONS, David M
• ZHIDONG XU
• UEMATSU, Kazutsugu
• MAZIERES, Julien
• MIKAMI, Iwao
• REGUART, Noemi
• MOODY, Terry W
• KITAJEWSKI, Jan
• MCCORMICK, Frank

Titel

Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells

Ist Teil von

• Oncogene, 2004-08, Vol.23 (36), p.6170-6174

Ort / Verlag

Basingstoke: Nature Publishing

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.