A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities

E-cadherin plays a critical role in many aspects of cell adhesion, epitheli al development, and the establishment and maintenance of epithelial polarit y. The loss of the adhesive function of E-cadherin is a critical step in th e promotion of epithelial cells to a more malignant phenotype. We identifie d a C/A single nucleotide polymorphism at -160 from the transcriptional sta rt site of the E-cadherin gene promoter. Transient transfection experiments showed that the A allele of this polymorphism decreased the transcriptiona l efficiency by 68% compared with the C allele (P < 0.001). Electrophoretic mobility shift and footprinting assays revealed that the C allele had a st ronger transcriptional factor binding strength than the A allele, These res ults indicate that the -160 C/A polymorphism has a direct effect on E-cadhe rin gene transcriptional regulation. This allelic variation may be a potent ial genetic marker that can help identify those individuals at higher risk for invasive/metastatic diseases.