Accession Number:

ADB249639

Title:

Role of ets Oncogenes in the Progression of Breast Cancer

Descriptive Note:

Annual rept. 30 Sep 97-29 Sep 98

Corporate Author:

THOMAS JEFFERSON UNIV PHILADELPHIA PA

Personal Author(s):

Report Date:

1998-10-01

Pagination or Media Count:

104.0

Abstract:

Our long term goal of this proposal was to study the role of elk-1 gene in the progression of breast cancer. Our studies on the expression of elk-1 in sporadic breast cancer suggests that changes in the levels of expression of elk-1 protein can lead to breast cancer. Elk-1 proteins were found to be involved in the estrogen induced signal transduction pathway and are targets for c-src kinase. Constitutive expression of elk-1 and elk-1 proteins in rat fibroblasts and human breast cancer cells induces apoptosis. Similarly, high level expression of BRCA1 protein in mouse fibroblasts and human breast cancer cells induces apoptosis on serum withdrawal or calcium ionophore treatment. These results suggest that elk-1 and BRCA1 genes play a critical role in the regulation of apoptosis of human breast cancer cells. We have found the BRCA1 protein to associate with E2F transcriptional factors, Cyclins, Cyclin dependent kinases, CBP and p53 protein suggesting a function for these proteins in cell cycle regulation, tumor suppression, transcription activation, etc. Breast cancers have a reduced ability to undergo cell death. Treatments aimed at increasing the apoptotic threshold by BRCA1 and elk-1 gene therapy may have the potential to prevent the progression of these cancers.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE