Accession Number : ADA321768

Title :   The Rap-1 Antioncogene in Breast Cancer.

Descriptive Note : Annual rept. 29 Aug 95-28 Aug 96,

Corporate Author : MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s) : Avruch, Joseph

PDF Url : ADA321768

Report Date : SEP 1996

Pagination or Media Count : 21

Abstract : This project aims to devise strategies to antagonize the promitogenic action of Ras and thereby suppress the transforming activity of the Erb B2 oncogenes found in 70% of human breast adenocarcinomas. The initial strategy was based on the ability of the Rap-1 GTPase when overexpressed, to suppress the malignant phenotype of V12 Ras transformed fibroblasts. It was anticipated that Rap-1 which shares an identical sequence corresponding to the primary Ras effector binding domain (amino acids (32-44), when overexpressed competes with Ras for critical mitogenic effects. In the past year, we have focused on the identification and characterization of proteins that interact with Rap-1 and Ras through their effector loop, in a GIP dependent fashion. We are attempting to ascertain whether the several proteins we have isolated that exhibit effector loop dependent binding to Rap-1 and Ras actually function as effectors for either Rap-1 or Ras, and whether they participate in regulation of the mitogenic activity of the cell in a positive or negative fashion. We have initially characterized the protein AF-6 because it was first isolated as a fusion partner of gene ALL-1, a chromosomal translocation found in acute leukemias. AF-6 binds to Ras and Rap-1 in a GTP dependent fashion, with a higher affinity for Rap-1. This contrasts with Raf, which prefers Ras. Future work will examine the ability of AF-6 and other candidate effectors to alter cell growth.

Descriptors :   *MITOSIS, *BREAST CANCER, CHROMOSOMES, IDENTIFICATION, FIBROBLASTS, CELLS(BIOLOGY), LOOPS, AMINO ACIDS, LEUKEMIA, TRANSLOCATION.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE