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N-Acetyltransferase 1 Polymorphism and Breast Cancer Risk
Annual rept. 29 Sep 2008-28 Sep 2009
LOUISVILLE UNIV FOUNDATION INC KY
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N-acetyltransferase 1 NAT1 catalyzes N-acetylation of aryl amine carcinogens resulting in their activation or inactivation. NAT110, NAT111 and NAT114, common variant alleles have been epidemiologically associated with increased risk for numerous cancers including breast. NAT1 is also upregulated in breast cancer. We employed a novel approach to study functional differences caused by NAT110 , NAT111, and NAT114 polymorphisms by using constructs that mimic complete human mRNAs. Plasmid constructs of NAT110 and NAT14 contained full length human mRNAs including either the NATa alternative promoter or NATb major promoter 5-UTR, the ORF, and 885 base pairs of the 3UTR region. Following transient or stable transfection into Chinese hamster ovary cells, NAT1-catalyzed N-acetylation of p-aminobenzoic acid was measured by HPLC and NAT1 protein expression was measured by Western blot. mRNA levels were studied using RT-PCR and polyA patterns by RNase Protection. No differences were observed in acetylation activity, protein levels, mRNA, or polyA patterns between NAT110, NAT111 and NAT14, but significant differences were seen between NAT114 and NAT14. Significant differences were also seen between all constructs containing the NATb 5 UTR compared to those containing the NATa 5 UTR.
APPROVED FOR PUBLIC RELEASE