SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers.

摘要: The functional single nucleotide polymorphism (SNP) in the MDM2 promoter region, SNP309, is known to be associated with various diseases, particularly cancer. Although many studies have been performed demonstrate mechanism of allele-specific expression (ASE) on they only utilized vitro techniques. It unknown whether ASE ascribed solely vivo. We attempted evaluate vivo using post-labeling followed by automated capillary electrophoresis under single-strand conformation conditions. For measuring a quantitative difference, we SNPs exons as markers, status which was heterozygous large population. To address cause beyond 20 %, confirmed sequences both MDM2-3’UTR and regions. assessed SNP might biomolecular interaction analysis luciferase assay. 20 % detected endometrial cancers, but not cancer-free endometria samples when an rs1690916 used marker. suspected that this cancer caused sequence heterogeneity MDM2-P2 promoter, found new polymorphism, labelled SNP55. There no difference between neither for SNP55 genotype frequencies nor allele frequencies, so, alone does affect risk. affected DNA binding affinity transcription factor Sp1 nuclear kappa-B (NFκB). Transcriptional activity P2 containing SNP55C suppressed NFκB p50 homodimers, SNP55T not. Only ASE-positive displayed localization p50. Our findings suggest are important transcriptional regulation cancers.