Accession Number:

ADA346658

Title:

Cell-Matrix Interactions in Breast Carcinoma Invasion.

Descriptive Note:

Annual rept. 15 Dec 96-14 Dec 97,

Corporate Author:

NEW YORK UNIV MEDICAL CENTER NY

Personal Author(s):

Report Date:

1998-01-01

Pagination or Media Count:

75.0

Abstract:

The alpha 6 beta 4 integrin is a laminin 5 receptor expressed on the basal, basement membrane-apposed surface of ductal breast epithelial cells. In contrast to all other known integrins, alpha 6 beta 4 is concentrated in hemidesmosomes, adhesive junctions which connect the basement membrane to the intracellular keratin cytoskeleton. In virtually all cases of human breast cancer analyzed, alpha 6 beta 4 has been found to be diffusely distributed at the cell surface instead of being concentrated in hemidesmosomes. Our previous studies have indicated that alpha 6 beta 4 promotes the assembly of hemidesmosomes by interacting, via a specific region of the large unique cytoplasmic domain of the beta 4 subunit, with cytoskeletal elements of hemidesmosomes. We have observed that ligation of the EGF-R or EGF-RNeu heterodimer promotes the association of the Src-family kinase Fyn with alpha 6 beta 4 and begun to map the sequences of Fyn and beta 4 required for the interaction. Ligation of the EGF-R or EGF-RNeu heterodimer causes tyrosine phosphorylation of the beta 4 tail and disassembly of hemidesmosomes.

Subject Categories:

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

Distribution Statement:

APPROVED FOR PUBLIC RELEASE