Differential Expression of DNA Double-Strand Break Repair Proteins in Breast Cells
Abstract
Two mechanisms that repair DNA double-strand breaks in mammalian cells are homologous recombination and non-homologous DNA end-joining (NHEJ). Previous studies showed that a critical component of the NHEJ pathway, the DNA-activated protein kinase (DNA-PK), was poorly expressed in non-lactating (resting) breast tissue. Therefore, we proposed to identify the mechanisms responsible for regulating levels of non-homologous end-joining DNA repair components in human breast tissue and to measure the DNA double-strand break repair capacity of breast epithelial cells. We reexamined the expression of DNA-PK in human breast tissues by immuno-histochemistry and extended these studies to two other components of the NHEJ repair pathway, XRCC4 and DNA ligase IV, as well as other DNA repair components including NBS 1 and MRE11. In contrast to the original report, 90% of the epithelial cells in normal resting breast tissues from 10 different patients expressed both components of DNA-PK, DNAPKcs and Ku. In contrast, stromal cells failed to express NHEJ proteins, but a cell line derived from breast stromal tissue did. No polymorphisms were detected in the Ku7O gene of 14 breast cancer patients, but 11.3% of breast cancer patients amplified the gene for the Wip1 phosphatase that regulates p53 activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408738
Entities
People
- Carl W. Anderson
- Mangale Tawde
Organizations
- Brookhaven National Laboratory