A Molecular Model for Repression of BRCA-1 Transcription by the Aryl Hydrocarbon Receptor
Abstract
The purpose of this project is to investigate whether or not expression of the BRCA-1 gene in breast epithelial cells exposed to polycyclic aromatic hydrocarbons (PAHs) is mediated by the aryl hydrocarbon receptor (AhR). The scope of the project is to examine whether or not the activated AhR alters BRCA-1 transcription through binding to several xenobiotic responsive elements (XRE) strategically located at -539 bp (CCGTFFAA=CyplAl-like) and +2Obase pairs (bp) (GCGTG=XRE-1) from the transcription start site on exon-lA. Two additional XREs (GCGTG) have been localized at -107 bp in the intervening sequence upstream (XRE-2) and +218 bp (XRE-3) into exon 1B. Findings of the experiments conducted in year 3 were: 1) Completed testing of truncation constructs for the BRCA-1 promoter region flanking XRE-3. 2) Investigated the effects of the Ahr ligands TCDD and alpha- naphthoflavone (ANF) on estrogen regulation of the BRCA-1 gene. 3) Investigated the cross- talk between the estrogen receptor and the AhR pathways. Results of these experiments indicate that XRE-3 is a negative regulator of BRCA-l transcription. Treatment with TCDD or ANF represses estrogen stimulation of BRCA-1 transcription suggesting that AhR ligands exert negative and effect on BRCA-1 expression. We also have gained evidence that the ER- alpha is recruited at the XREs flanked in the BRCA-l promoter.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418719
Entities
People
- Donato F. Romagnolo
Organizations
- University of Arizona