Oncogenic Beta-Catenin Targeted Human Cancer Cells for Identification and Testing of Novel Anticancer Drugs
Section: For Industry
Categories: "Research Tools"
Reference #: 2001-030
OTC Contact: Tracy Bruehs, M.S., J.D. (Directory Information | Send a Message)
Description
A set of isogenic human colon cancer cells (HCT116) genetically identical except for the presence or complete absence of their endogenous wild-type or mutational activated B-catenin gene. Activation of B-catenin is a critical step in the pathogenesis of many human cancers and is the initiating event in adenocarcinoma of the colon. Activated B-catenin, therefore, is a critical oncogenic stimulus throughout the progression of human colon cancer and is a useful target for screening small molecule inhibitors of activated B-catenin.
Applications
Human somatic cell gene targeting to create an isogenic set of human colon cancer cells that differ only in the presence or absence of their endogenous wild-type or activated B-catenin gene. Such cells are well suited as a molecular target for development of anticancer pharmaceuticals. These cells can be used in high throughput screens to identify novel B-catenin targeted agents and for secondary screens to test inhibitors identified in in-vitro assays.Advantages
- Parental cells and cells retaining oncogenic B-catenin but deleted for wild-type B-catenin serve as ideal isogenic controls allowing identification and testing of compounds with specific activity towards cancer cells with oncogenic B-catenin
- The cells are created by gene targeting (rather than siRNA/shRNA), resulting in complete abrogation of oncogene expression
- Because activation of B-catenin provides a gain-of-function, specific pharmacological inhibition of activated B-catenin has been shown to reverse the tumorigenic properties of human cancer cells, and therefore, form the basis of an effective anticancer strategy.
Stage of Development
Development completed; ready for licensing.Relevant Publications
Kim JS, Crooks H, Dracheva T, Nishanian TG, Singh B, Jen J, Waldman T. Oncogenic B-Catenin is Required for BMP4 Expression in Human Cancer Cells. Cancer Research 62:2744, 2002.
Kim JS, Crooks H, Foxworth A, Waldman T. B-Catenin is a Valid Molecular Target for the Development of Pharmacological Inhibitors. Molecular Cancer Therapeutics 1:1355, 2002.
INVENTOR: Todd Waldman, M.D., Ph.D.
