(ALPHA)2(BETA)1 Integrin-Induced Breast Cancer Differentiation.
Abstract
Cell-extracellular matrix (ECM) interaction is important for cell differentiation in mammary epithelial cells. Previous reports suggest that alpha2Beta1 integrin, a collagen/laminin receptor, plays a critical role in normal mammary cell differentiation as well as in the pathogenesis of breast cancer. Therefore, the modulation of alpha2Beta1-ligand interaction can be a key factor in controlling breast cancer differentiation. The purpose of this study is to clarify the role of alpha2Beta1-ligand interaction in breast cancer differentiation, and to elucidate the molecular mechanism of alpha2Beta1-ligand interaction. During the second year of this project, I found that several discontinuous amino acid residues surrounding the MIDAS (metal ion dependent adhesion site) motif in the alpha2 1(A) domain are critical for collagen binding. In contrast, mutation or deletion of the entire unique C-helix residues, which have previously been predicted to determine collagen binding specificity, did not affect collagen binding at all. We created a collagen/alpha2 I domain docking model. in this model, Asn-154, Tyr-157, Asp-219, and His-258 make direct contact with collagen. These findings will form the basis for the remainder of this study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA377910
Entities
People
- Tetsuji Kamata
Organizations
- Scripps Research