Breast Cancer: Involvement of Epidermal Growth Factor Receptor, MDM2, and p53 Mutations.
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1996
- Accession Number
- ADA321579
Entities
People
- John Meyers
Organizations
- University of Texas Health Science Center at San Antonio