Accession Number:

ADB215863

Title:

Role of Integrin Related Tyrosine Kinases in Growth Control of Normal and Tumorigenic Human Mammary Epithelium.

Descriptive Note:

Annual rept. 1 Jul 95-30 Jun 96,

Corporate Author:

SCRIPPS RESEARCH INST LA JOLLA CA

Personal Author(s):

Report Date:

1996-07-01

Pagination or Media Count:

47.0

Abstract:

We are attempting to identify integrin-specific signalling events that may contribute to malignant transformation in mammary epithelium. We are focusing on the extracellular matrix protein Iaminin-5r, which is located in mammary epithelial basement membrane. We hypothesize that binding of integrins to laminin-5r elicits downstream signalling events that may help define the normal phenotype of mammary epithelial cells disruption of these signals may contribute to the development of malignancy. To date, we have established that normal and malignant cell lines plated on laminin-5r differ in at least three ways normal and malignant cells use different integrin receptors to bind laminin-5, malignant cells migrate while normal cells do not, and normal and malignant cells exhibit different patterns of tyrosine phosphate-containing proteins following binding to laminin-5. The integrins that mediate these responses have been identified in two cell types, and we hypothesize that in these two cells, the conversion from normal to malignant phenotype involves the activation of the a3Beta1 integrin. Our goals for the upcoming year are to further elucidate the signalling pathways associated with the alpha 3Beta1 integrin following binding of laminin-5r, and to identify functionally active regions of laminin-5r responsible for eliciting these effects.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE