Accession Number:

ADA370154

Title:

B-Catenin Stability in Breast Cancer

Descriptive Note:

Annual rept. 15 Jun 97-14 Jun 98

Corporate Author:

GEORGETOWN UNIV WASHINGTON DC

Personal Author(s):

Report Date:

1998-07-01

Pagination or Media Count:

15.0

Abstract:

Beta-catenin is a critical signaling molecule that participates in differentiation and proliferation pathways. Beta-catenin binds the HMG-box transcription factor LEF-l, to directly regulate gene transcription. The tumor suppressor adenomatous polyposis coli APC gene product has been reported to associate with beta-catenin and effect its down- regulation by an unknown mechanism. We hypothesize that APC helps target beta-catenin to proteasomal degradation. We tested our hypotheses in vivo by transient transfections of colon cancer cells with various APC deletion constructs, followed by treatment with proteasome-specific inhibitors. The LEF-reporters TOPFLASH and FOPFLASH were used to demonstrate a role for APC in regulating beta-catenin-LEF signaling via the ubiquitin- proteasome pathway. Surprisingly, lithium that inhibits GSK3 beta also was found not to reverse the ability of APC to down-regulate LEF signaling.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE