Breast Cancer: Involvement of Epidermal Growth Factor Receptor, MDM2, and p53 Mutations.
Abstract
Here we describe our analysis of the domain requirements for mutant p53 to transactivate promoters of the human epidermal growth factor receptor (EGFR), human multiple drug resistance 1 (MDR-1) and human proliferating-cell nuclear antigen (PCNA) genes. We also report the identification of a structural domain required for the "gain of function" property of mutant p53-281G. "Gain of function" is measured as the tumorigenicity (in nude mice) of 10(3) murine cells expressing mutant p53 constitutively. We have generated internal deletion mutants of p53-281G deleting conserved domains I, II, III, IV, and V, individually. All these mutants have significantly activated the PCNA promoter, suggesting that the mechanism of transactivation of the PCNA promoter is different from that of the EGFR and MDR-1 promoters. When expressed constitutively in 10(3) cells, p53-281G del 393-327 was found to be defective in inducing tumor formation in nude mice although intact p53-281G was very efficient. Thus, our results suggest that structural domains near the C-terminus are needed for "gain of function".
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1998
- Accession Number
- ADA349600
Entities
People
- Arpad Lanyi
Organizations
- University of Texas Health Science Center at San Antonio