Oxidases as Breast Cancer Oncogens
Abstract
This proposal tests a novel concept that H2O2 generating oxidase-mediated production of reactive oxygen species in breast epithelium contributes to the development of breast cancer. Two tasks are currently being pursued. The first deals with the overexpression of xanthine oxidase (XOX) or urate oxidase (UOX) in a non-tumorigenic human mammary epithelial cell line to ascertain whether oxidase overexpressing cells undergo transformation when exposed to substrate xanthine for XOX and uric acid for UOX. We have made constructs to express these oxidases under the direction of cytomegalovirus or mouse mammary tumor virus (MMTV) promoter. Transfections are being perlormed to generate cell lines stably expressing these enzymes. The second task deals with the generation and characterization transgenic mice expressing UOX under the transcriptional control of MMTV promoter, an in vivo model system to explore the role of oxidative stress in mammary carcinogenesis. The choice for urate oxidase is based on the fact that we have used this enzyme in previous studies showed that cells stably expressing this enzyme reveal the characteristic crystals of this enzyme in peroxisomes. We have injected the construct in fertilized ova and have identified five founder mice. These are being bred to ascertain germ line transmission and expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA386441
Entities
People
- Anjana V. Yeldandi
Organizations
- Northwestern University