The expression of a member of the Ah gene battery family, CYP1A1, has been extensively used as a potential biomarker of exposure to """"""""dioxin-like"""""""" substances and as a negative prognostic indicator for breast cancer. Results of several studies using human breast cancer cell lines as models have demonstrated that basal and inducible expression of CYP1A1 is regulated in part by the estrogen receptor (ER). The objective of the proposed experiments is to investigate the mechanism(s) of interaction between the ER and the AhR-Arnt complex. Molecular biological techniques will be utilized to evaluate the possibility that 1) there is direct interaction between the AhR-Arnt complex and the ER 2) the ER interacts with DNA and/or the AhR complex 3) ER associate proteins associate with the AhR complex and act as inhibitors of gene expression or 4) there are common proteins which bind to the AhR or Arnt and the ER. Since these target genes are used as prognostic indicators of several cancers, the results of these studies will identify molecular determinants which may link basal and inducible gene expression with disease outcomes.
