title: The E-cadherin -347G->GA promoter polymorphism and its effect on transcriptional regulation.
abstract: E-cadherin plays a critical role in epithelial cell-cell adhesion and maintenance of tissue architecture. Loss of E-cadherin expression in humans has been associated with cancer, and a number of cancer-related mutations have been identified. Here, we sought to investigate whether the -347G-->GA single nucleotide polymorphism affects the transcriptional activity of the E-cadherin gene. First, we measured the promoter activity of the -347G-->GA polymorphism using a dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The dual luciferase reporter assay showed that the GA allele decreased the transcriptional efficiency by 10-fold (P < 0.001) compared with the G allele. Similarly, EMSA revealed that the GA allele had a weak transcription factor binding strength compared with the G allele. We then examined the frequency of this polymorphism in familial gastric cancer (FGC) patients by denaturing high-performance liquid chromatography. We found that the E-cadherin genotype (-347G/GA heterozygous or GA homozygous) was associated with FGC patients (P < 0.05) compared with the G homozygous genotype. Taken together, these results suggest that the GA allele may cause weak transcription factor binding affinity and low transcriptional activity in E-cadherin expression.
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Center and Cancer Research Institute, Seoul National University, South Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shin
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hye-Rin
authors.initials: HR
authors.lastname: Park
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Park
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Park
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Kyong-Ah
authors.initials: KA
authors.lastname: Yoon
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
mesh_terms: D000483:Alleles; D015820:Cadherins / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D005787:Gene Frequency; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D015820:Cadherins