Accession Number : ADA303186

Title :   Breast Cancer: Involvement of Epidermal Growth Factor Receptor, MDM2 and P53 Mutations.

Descriptive Note : Annual rept. 15 Sep 94-14 Sep 95,

Corporate Author : TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO

Personal Author(s) : Ludes-Meyers, John H.

PDF Url : ADA303186

Report Date : OCT 1995

Pagination or Media Count : 31

Abstract : The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with an extracellular epidermal growth factor (EGF)-binding domain and an intracellular protein tyrosine kinase domain. EGF stimulates cell proliferation by directly activating EGFR, leading to signal transduction through an intracellular cascade of second messengers. It was previously demonstrated that the wild-type human pS3 tumor suppressor can transactivate the human EGFR promoter through a p53-response element mapped to the region from -569 to -104, relative to the translational start site. Further analysis has identified the 27-base pair region from -265 to -239 as the p53-binding site/response element. This region possesses sequence homology to a p53- binding site/response element in the human retinoblastoma susceptibility (Rb) gene promoter, and is responsive to wild-type pS3 when cloned upstream of a minimal heterologous promoter. Mobility-shift and DNase I footprinting assays indicated that wild-type pS3 binds directly to the response element. The p53-binding site/response element overlaps the binding sites for both positive (ETF) and negative (GCF) regulators of EGFR promoter activity, and contains or borders the most 5' of the EGFR in vivo transcriptional start sites.

Descriptors :   *MUTATIONS, *RECEPTOR SITES(PHYSIOLOGY), *EPIDERMIS, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, GROWTH(GENERAL), SITES, RESPONSE, SIGNALS, CLONES, TRANSDUCERS, BINDERS, CELLS(BIOLOGY), SENSE ORGANS, CANCER.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE