Function of the Alpha6 in Breast Carcinoma.
Abstract
During the first year of this award, we established that the a6% 1 integrin plays an important role in regulating the growth and survival of breast carcinoma. We developed a dominant negative strategy to 'knock-out' the expression of the oc6% 1 integrin in a highly metastatic breast carcinoma cell line (MDA-MB-435). After depletion of a6%l surface expression, these cells are deficient in their growth in the mammary fat pad of athymic mice and can no longer survive as metastases in the lungs and liver. We also established a mechanism for the involvement of the a6%4 integrin in promoting carcinoma invasion. We isolated MDA-MB-435 transfectants that express the %6%4 integrin receptor. These cells have a marked increase in their ability to invade through basement membrane matrices in vitro. The mechanism by which this integrin promotes invasion involves a preferential and localized targeting of phosphoinositide-3 OH kinase (PI 3-K) activity. The small GTP-binding protein Rac is downstream of PI 3-K in the cells examined and it is involved in invasion. These findings establish a novel function for PI 3-K signaling and suggest that this a6%4/PI 3-K signaling pathway is a potential target for inhibiting tumor spread.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA335982
Entities
People
- Arthur M Mercurio
Organizations
- Beth Israel Deaconess Medical Center