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.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Kim JS,Crooks H,Foxworth A,Waldman Tkeywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
1355-9issue
14eissn
1535-7163issn
1538-8514journal_volume
1pub_type
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
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