Mechanisms of Breast Carcinogenesis Involving Wild-Type p53
Abstract
This research application is centered on testing the hypothesis that there are mechanisms of carcinogenesis involving functional inactivation of wild-type p53 besides direct genetic alteration in human breast cancer. The goal of this proposal is to identify mechanisms and clone genes which encode proteins which act on wild-type p53 and functionally inactivate it. Technical objectives include: (1) Determine the mechanisms by which rat embryo fibroblasts acquire resistance to the growth suppressing activity of p53 (2) Elucidate the underlying mechanism for cytoplasmic localization of wild-type p53 in particular breast tumor cell lines. (3) Utilize an expression cloning strategy to screen for novel regulators of p53 function. (4) Determine the relevance of these various mechanisms in human breast cancer. The overexpression or mutational activation of such genes will then be examined in human breast tumors to determine whether the genes encoding such proteins are indeed involved in novel mechanisms of carcinogenesis. Such approaches as outlined here can address two important issues. The first is to determine whether overexpression of certain regulators of p53 may be associated with a particular prognosis or a particular success rate for a type of therapy. Second, identification of relevant regulators of p53 can allow us to begin to use such protein-protein complexes as targets for therapeutic intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA383031
Entities
People
- James J. Manfredi
Organizations
- Icahn School of Medicine at Mount Sinai