Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors.

Abstract

Activation of beta-catenin is a critical step in the pathogenesis of many common human cancers and is the initiating event in adenocarcinoma of the colon. Because activation of beta-catenin provides a gain-of-function, it is tempting to speculate that specific pharmacological inhibition of activated beta-catenin might reverse the tumorigenic properties of human cancer cells and therefore form the basis of an effective anticancer strategy. In an effort to provide proof-of-principle for such a strategy, we used a novel clonal growth assay based on human somatic cell gene targeting to determine whether activated beta-catenin remains a necessary oncogenic stimulus in advanced human cancer cells. Using this approach, we demonstrate that beta-catenin is a necessary oncogene in human SW48 and DLD1 colon cancer cells but not in HCT116 cells. These data indicate that activated beta-catenin can remain a critical oncogenic stimulus throughout the progression of human colon cancer and suggest that the small molecule inhibitors of activated beta-catenin currently under development will be effective anticancer therapeutics in a subset of malignant colon cancers.

3 Figures and Tables

050'04'06'08'10'12'14'16
Citations per Year

220 Citations

Semantic Scholar estimates that this publication has 220 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Kim2002ProofofprincipleOB, title={Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors.}, author={J. Julie Kim and Heather Crooks and Aaron Foxworth and Todd Waldman}, journal={Molecular cancer therapeutics}, year={2002}, volume={1 14}, pages={1355-9} }