Accession Number : ADA321579

Title :   Breast Cancer: Involvement of Epidermal Growth Factor Receptor, MDM2, and p53 Mutations.

Descriptive Note : Annual rept. 15 Sep 95-14 Sep 96,

Corporate Author : TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO

Personal Author(s) : Meyers, John

PDF Url : ADA321579

Report Date : OCT 1996

Pagination or Media Count : 19

Abstract : The human epidermal growth factor receptor (EGFR) promoter is activated by both wild-type and tumor-derived mutant p53. In this report we demonstrate that the EGFR promoter is activated by tumor-derived p53 mutants p53-143A, p53-175H, p53-248W, p53-275H and p53-281G. Using p53-281G as a model we show that the transactivation by mutant p53 requires different protein domains than wild-type p53 and does not require the wild-type p53-binding site. The minimal EGFR promoter from positions -104 to -20 which does not contain the wild-type p53-binding site is transactivated by the p53 mutants but not wild-type protein. Together the domain requirements and promoter sequence requirements indicate a difference in the mechanism of transactivation by wild-type and mutant p53. Transactivation of the EGFR promoter by mutant p53 may represent a mechanism by which tumor cells lose cell growth control.

Descriptors :   *NEOPLASMS, *RECEPTOR SITES(PHYSIOLOGY), *GROWTH(PHYSIOLOGY), *BREAST CANCER, CONTROL, REQUIREMENTS, SEQUENCES, CELLS(BIOLOGY), SENSE ORGANS, EPIDERMIS.

Subject Categories : Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE