title: The suppression of colon cancer cell growth in nude mice by targeting beta-catenin/TCF pathway.
abstract: The adenomatous polyposis coli (APC) or beta-catenin genes are frequently mutated in colorectal cancers, leading to activation of downstream genes with beta-catenin/T-cell factor (Tcf)-responsive promoters. We have developed a gene therapy approach selectively targeting colorectal cancer cells in which beta-catenin/Tcf4 pathway is activated by using a recombinant adenovirus AdTOP-CMV-TK, which carries a herpes simplex virus thymidine kinase gene (HSV TK) under the control of a beta-catenin/Tcf-response promoter linking to a minimum CMV promoter. AdTOP-CMV-TK and ganciclovir (GCV) treatment significantly suppressed the growth of human DLD-1 colon cancer cells in nude mice. Furthermore, no significant tumor suppression effect was observed in human hepatoma cell line SK-HEP-1, in which the beta-catenin/Tcf pathway is not activated, as a control experiment. In summary, we demonstrated the selective targeting of colorectal cancers with activated beta-catenin by AdTOP-CMV-TK and GCV treatment in animal models, as well as its therapeutic potential for colon cancer metastasized to liver.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA.
authors.forename: Ka Yin
authors.initials: KY
authors.lastname: Kwong
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Zou
authors.forename: Chi-Ping
authors.initials: CP
authors.lastname: Day
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D000818:Animals; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003587:Cytomegalovirus / Q000201:enzymology / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D013937:Thymidine Kinase / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D007376:Interleukin-2; D015534:Trans-Activators; D051176:beta Catenin; D013937:Thymidine Kinase