Accession Number:

ADA364255

Title:

Regulation of Breast Carcinoma Progresssion by the Integrins.

Descriptive Note:

Annual rept. 1 Sep 97-31 Aug 98,

Corporate Author:

BETH ISRAEL HOSPITAL BOSTON MA

Personal Author(s):

• Shaw, Leslie M.

Report Date:

1998-09-01

Pagination or Media Count:

23.0

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-11 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.

Descriptors:

• *CELLS(BIOLOGY)
• *METASTASIS
• *BREAST CANCER
• CONTROL
• ACTIVATION
• SURVIVABILITY
• GROWTH(GENERAL)
• NEOPLASMS
• LIFE CYCLES
• MAMMARY GLANDS

Subject Categories:

• Medicine and Medical Research
• Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE