Role of p120ctn in Cadherin Mediated Suppression of Breast Cancer
Abstract
This research aims to understand the mechanism by which the catenin p120 regulates the cell adhesion molecule E-cadherin, a protein whose function is critical to inhibiting metastasis of human tumors. My hypothesis is that uncoupling p120 from E-cadherin by mutation of the juxtamembrane domain will result in an E-cadherin molecule that is defective for the function contributed by pl 20. In this reporting period, I have mutated the p120 binding site on E-cadherin and generated minimally altered E-cadherin proteins that are selectively unable to bind p120. Expression of the p120- uncoupled cadherin proteins in the E-cadherin deficient human breast cancer cell line MDA231 eliminates the ability of E-cadherin to induce tightly organized epithelial colonies. The cells form poor junctions and are not able to mediate strong cell-cell adhesion, We are planning to analyze the metastatic potential of these cells in mice. These results significantly clarify the role of pt2O in cadherin function and could ultimately lead to rational therapeutic approaches to inhibit metastasis of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396644
Entities
People
- Albert B. Reynolds
- Molly A. Thoreson
Organizations
- Vanderbilt University Medical Center