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 loss of 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 AhR complexed with the AhR-nuclear transporter (ARNT) protein, binds to several xenobiotic responsive elements (XRE) strategically located at -539 bp (CCGTGGAA=Cyp1A1-like) and +20base pairs (bp) (GCGTG=XRE-1) from the transcription start site on exon-1A. 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 these experiments were: 1) Confirmed in transfection experiments(a)pyrene represses transcription at the BRCA-1 promoter; 2) Developed mutation constructs for CYP1A1, XRE-1, XRE-2 and double and triple mutants; 3) Developed deletion constructs for CYP1A1, XRE-1 and XRE-2; 4) Observed that the CYP1A1 element may be required (positive element) for constitutive activity of the BRCA-1 promoter and that the XRE-1 and XRE-2 may be negative cis-acting elements on basal BRCA-1 transcription. Finally, we report that the XRE-1 may act as a repressor of BRCA-1 transcription under conditions of estrogen stimulation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396170
Entities
People
- Donato F. Romagnolo
Organizations
- University of Arizona