Accession Number:

ADA383962

Title:

Regulation of Breast Carcinoma Progression by the Alpha-6 Integrins

Descriptive Note:

Annual rept. 1 Sep 1998-31 Aug 1999

Corporate Author:

BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA

Personal Author(s):

Report Date:

1999-09-01

Pagination or Media Count:

73.0

Abstract:

During the second year of this career development award, we have continued to make progress in determining the contribution of the alpha6 integrin receptors to breast carcinoma progression. In previous work we had established that the alpha6Beta4 receptor contributes to the growth and survival of breast carcinoma metastases. In addition, we had demonstrated that de novo expression of the integrin Beta4 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 alpha6Beta4 integrin to promote carcinoma invasion is related to its activation of phosphoinositide 3-OH kinase PI3K and the small GTP-binding protein Sac. We have also identified PKC-epsilon as a critical effector for invasion and we have determined that it contributes to cell motility through the regulation of lamellae organization and function. We have begun to investigate how PI3K is activated by the alpha6Beta1 and alpha6Beta4 integrins. We have preliminary evidence to support that alpha6Beta4 cooperates with a cell surface protein for this activation. Additional signaling molecules that we are investigating that may play a role in alpha6-dependent functions are pl3Ccas and the tyrosine phosphatase SHP-2. An alpha6-specific ribozyme has been constructed.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE