The Role of AhR in Breast Cancer Development
Annual summary rept. 1 Jul 2003-30 Jun 2006
BOSTON UNIV MA
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The aryl hydrocarbon receptor AhR is an environmental carcinogen-activated transcription factor associated with tumorigenesis. Little is known of the transcriptional consequences of constitutive AhR activation. The effects of constitutively active and environmental ligand-induced AhR on c-myc, an oncogene, were investigated. Results indicate that 1 the AhR constitutively binds the c-myc promoter 2 there is a low but significant baseline level of c-myc promoter activity, which is not regulated by NF-kappaB and is not affected by an environmental AhR ligand 3 deletion of any one of the AhREs has no effect on constitutive reporter activity, while deletion of all six increases reporter activity approximately fivefold 4 a similar increase in reporter activity occurs when constitutively active AhR is suppressed by transfection with an AhR repressor plasmid AhRR 5 AhRR transfection significantly increases background levels of endogenous c-myc mRNA and c-Myc protein. These results suggest that the AhR influences the expression of c-Myc, a protein critical to malignant transformation.
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