P53 Regulation of Uridine Phosphorylase Activity, Pyrimidine Salvage Pathway and Their Effects on Breast Cancer Therapy
Abstract
This research project has been focused on the elucidation of the mechanism affecting the therapeutic efficacy of fluoropyrimidines to improve the clinical outcome of cancer patients. Based on the findings of the last scientific year that the nullification in ES cells of uridine phosphorylase (UPase) leads to a significantly increased cell resistance to fluoropyrimidines and that wild-type p53 protein down-regulates UPase expression, we have focused this year's scientific research on the following two areas: 1) Elucidation of the p53 regulation mechanism(s) of UPase expression; In this investigation, we demonstrated that wild-type p53 protein represses UPase gene expression via sequence specific DNA binding at promoter level, and that the mutation of p53 leads to loss of this regulatory function. 2) In vivo study of UPase function in fluoropyrimidine metabolism and uridine regulation. In order to better translate the basic research understanding to the clinical service, we have extended our first year's findings in UPase knockout ES cell to in vivo study using the UPase knockout mouse model generated. The research results defined in vivo the important role of UPase in fluoropyrimidine metabolism and uridine regulation in plasma and tissue.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407128
Entities
People
- Deliang Cao
- Giuseppe Pizzorno
Organizations
- Yale University