Effect of a Single Nucleotide Polymorphism (NP) on Breast Cancer Invasion
Abstract
The lethality of breast cancer is derived from its ability to metastasize, and matrix metalloproteinases (MMPs) facilitate cellular invasion by degrading the extracellular matrix. One component of MMP regulation is transcription. We have identified a single nucleotide polymorphism (SNP) that enhances the transcriptional activity of MMP-l promoters in transient transfections. The SNP consists of an extra guanine nucleotide that creates an ETS family transcription factor binding site (2G). We utilized cotransfection experiments, and determined that MMP-l promoters containing the 2G polymorphism can interfere with transcriptional activity of promoters with the lG polymorphism, 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. To better address the role of the polymorphism in endogenous gene expression, more samples are needed, and a source of those samples is human foreskin fibroblasts (HFFs). Initial experiments in HFFs have begun, but the amount of data currently limits statistical analysis. Future experiments include real time RT-PCR assays to better quantitate MMP-1 RNA in at least 50 HFF lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396491
Entities
People
- Colby A. Wyatt
- Constance E. Brinckerhoff
Organizations
- Dartmouth College