[Frontiers in Bioscience 11, 2759-2766, September 1, 2006]

Uridine phosphorylase in breast cancer: a new prognostic factor?

Ruilan Yan 1, Laxiang Wan 2, Giuseppe Pizzorno 2, 3, and Deliang Cao1

1 Department of Medical Microbiology, Immunology, and Cell Biology, Cancer Institute, Southern Illinois University School of Medicine, 911 North Rutledge Street, Springfield, IL 62702, 2 Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, 3 Division of Drug Development, Nevada Cancer Institute, 10441 West Twain Boulevard, Las Vegas, NV 89117

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Transcriptional regulation of uridine phosphorylase expression
4. Fluoropyrimidine activation by uridine phosphorylase
4.1. Activation of 5-fluorouracil and 5'-deoxy-5-fluorouridine
4.2. Activation of capecitabine, a novel prodrug of 5-fluorouracil
5. Uridine phosphorylase induction in mammalian tumors
6. Uridine phosphorylase and breast cancer
7. Summary and perspective
8. References

1. ABSTRACT

Uridine phosphorylase (UPase) is an enzyme that converts the pyrimidine nucleoside uridine into uracil. Upon availability of ribose-1-phosphate, UPase can also catalyze the formation of nucleosides from uracil as well as from 5-fluorouracil, therefore involved in fluoropyrimidine metabolism. UPase gene expression is strictly controlled at the promoter level by oncogenes, tumor suppressor genes, and cytokines. UPase activity is usually elevated in various tumor tissues, including breast cancer, compared to matched normal tissues and this induction appears to contribute to the therapeutic efficacy of fluoropyrimidines in cancer patients. In this review, we will discuss in detail the role of UPase in the activation of fluoropyrimidines and its effect on the prognosis of breast cancer patients.