Targeted suppression of beta-catenin blocks intestinal adenoma formation in APC Min mice.

Journal Article (Journal Article)

INTRODUCTION: Mutations involving the adenomatous polyposis coli (APC) tumor suppressor gene leading to activation of beta-catenin have been identified in the majority of sporadic colonic adenocarcinomas and in essentially all colonic tumors from patients with Familial Adenomatous Polyposis. The C57BL/6J-APC(min) (Min) mouse, which carries a germ line mutation in the murine homolog of the APC gene is a useful model for intestinal adenoma formation linked to loss of APC activity. One of the critical downstream molecules regulated by APC is beta-catenin; molecular targeting of beta-catenin is, thus, an attractive chemopreventative strategy in colon cancer. Antisense oligodeoxynucleotides (AODNs) capable of downregulating murine beta-catenin have been identified. ANALYSIS OF beta-CATENIN PROTEIN EXPRESSION IN LIVER TISSUE AND INTESTINAL ADENOMAS: Adenomas harvested from mice treated for 7 days with beta-catenin AODNs demonstrated clear downregulation of beta-catenin expression, which was accompanied by a significant reduction in proliferation. There was no effect on proliferation in normal intestinal epithelium. Min mice treated systemically with beta-catenin AODNs over a 6-week period had a statistically significant reduction in the number of intestinal adenomas. These studies provide direct evidence that targeted suppression of beta-catenin inhibits the formation of intestinal adenomas in APC-mutant mice. Furthermore, these studies suggest that molecular targeting of beta-catenin holds significant promise as a chemopreventative strategy in colon cancer.

Full Text

Duke Authors

Cited Authors

  • Foley, PJ; Scheri, RP; Smolock, CJ; Pippin, J; Green, DW; Drebin, JA

Published Date

  • August 2008

Published In

Volume / Issue

  • 12 / 8

Start / End Page

  • 1452 - 1458

PubMed ID

  • 18521697

Electronic International Standard Serial Number (EISSN)

  • 1873-4626

Digital Object Identifier (DOI)

  • 10.1007/s11605-008-0519-6


  • eng

Conference Location

  • United States