The E-cadherin −347G→GA promoter polymorphism and its effect on transcriptional regulation

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.