Selective targeting to the hyperactive beta-catenin/T-cell factor pathway in colon cancer cells.
Many colon cancers suffer mutations in either the adenomatous polyposis coli or beta-catenin genes that lead to stabilization of beta-catenin and activation of downstream T-cell factor (Tcf) target genes. We have developed a novel approach targeting colon cancer cells based on their aberrant beta-catenin/Tcf signaling pathway. A recombinant adenovirus, in which an apoptosis gene fadd is under the control of the promoter containing Tcf-responsive elements, selectively and efficiently kills colon cancer cells in which the beta-catenin/Tcf pathway is hyperactivated. Our data therefore provide a conceptual proof that aberrantly activated Wnt/beta-catenin/Tcf pathways can be used to selectively target colon cancers.
Chen
R H
RH
Cancer Research Institute, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94115, USA.
McCormick
F
F
D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin