B-Catenin Stability in Breast Cancer
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA370154
Entities
People
- Stephen Byers
- Vijay Easwaran
Organizations
- Georgetown University