Effect of a Single Nucleotide Polymorphism (NP) on Breast Cancer Invasion
Abstract
This study took several approaches to determine the influence of a single nucleotide polymorphism (SNP) in the matrix metalloproteinase 1 promoter on gene transcription in normal and breast cancer cell lines or tissue. The SNP consists of an extra guanine nucleotide that creates an ETS family transcription factor binding site (2G), and we previously demonstrated that the 2G SNP leads to an increase in transcriptional activity of the MMP-l promoters containing the 2G SNP can interfere with transcriptional activity of promoters with the 1G SNP, but only at high concentrations of DNA. Analysis of five breast cancer cell lines with transient transfections reveals that the transcriptional effect of the 2G SNP is only observed in one cell line, and this cell line was the only one examined that expressed endogenous MMP-l. The influence of the SNP on endogenous MMP-1 expression was examined in 34 human foreskin fibroblasts (HFFs). From these data we can conclude that the MMP-l promoter genotype of normal fibroblasts is not predictive of MMP-1 expression. The SNP genotypes of 35 breast cancer patients were determined, and from these data, we can conclude that the SNP has no influence on MMP-1 production from diseased breast tissue. We can block MMP-l production using short interfering RNA (siRNA) molecules, and have developed a powerful tool to determine the importance of MMP-1 in an in-vivo model of breast cancer metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418964
Entities
People
- Colby A. Wyatt
- Constance E. Brinckerhoff
Organizations
- Dartmouth College