Molecular Model for Repression of BRCA-1 Transcription by the Aryl Hydrocarbon Receptor.

摘要

The purpose of this project is to investigate whether or not regulation 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 the experiments conducted during the lest period include: (1) Completed testing of mutation contructs for XRE2 and investigated the effects of antagonists of the AhR and ER-alpha on regulation of BRCA-1 transcription by estrogen and the dioxin-like compound TCDD in breast cancer MCF-7 cells. (2) Characterized the mechanism of interaction between the ER-alpha and the AhR at the XRE-2 by chromatin immunoprecipitation assay (ChIP).