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(ALPHA)2(BETA)1 Integrin-Induced Breast Cancer Differentiation
Annual report 1 Aug 97-31 Jul 98
SCRIPPS RESEARCH INST LA JOLLA CA
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Cell-extracellular matrix ECM interaction is important for cell differentiation in mammary epithelial cells. This cell-ECM interaction is mediated by integrins, a family of cell adhesion receptors that mediate cell-cell and cell-ECM interactions, and play a critical role in cell migration, proliferation, and differentiation. The integrin alpha 2 beta 1 functions as a collagen andor laminin receptor. Previous reports suggest that alpha 2 beta 1 plays a critical role in normal mammary cell differentiation as well as in the pathogenesis of breast cancer. Therefore, alpha 2 beta 1 -ligand interaction can be a key factor in controlling breast cancer differentiation. The purpose of this study is to clarify the role of alpha 2 beta 1 -ligand interaction in breast cancer differentiation, and to elucidate the molecular mechanism of alpha 2 beta 1 -ligand interaction. During the first year of this project, I found that 1 ligand binding-defective mutant alpha 2 can be stably expressed in a poorly differentiated mammary carcinoma cell line, Mm5MT, and 2 the collagen-contact sites in alpha 2 beta 1 are localized in the three separate loop structures surrounding the MIDAS metal ion dependent adhesion site motif in the IA domain of alpha 2. These findings will form the basis for the remainder of this study.
APPROVED FOR PUBLIC RELEASE