Regulation of Breast Carcinoma Progresssion by the Integrins.
Abstract
During the first year of this career development award, we have made progress in determining the contribution of the alpha-6 integrin receptors to breast carcinoma progression. In previous work we had established that the alpha-6-Beta-1 receptor contributes to the growth and survival of breast carcinoma metastases. In addition, we had demonstrated that de novo expression of the integrin Beta-4 subunit in breast carcinoma cell lines that lack this integrin subunit increases their invasive potential. Since submitting the initial proposal, we have demonstrated that the ability of the alpha-6-Beta-4 integrin to promote carcinoma invasion is related to its activation of phosphoinositide 3-OH kinase (PI3K) and the small GTP-binding protein Rac. In the past year we have identified PKC-epsilon as a critical effector for invasion and we will continue to investigate how this kinase contributes to this complex process. In addition we have identified a cooperative action of alpha-6-Beta-1%1 with an important survival growth factor, IGF-1. Interestingly, our data indicate that the activation of PI3K appears to be an essential component of both alpha-6-dependent pathways and this underscores the importance of understanding in more detail how this lipid kinase is activated and which downstream effectors are involved.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA364255
Entities
People
- Leslie M. Shaw
Organizations
- Beth Israel Deaconess Medical Center