Lc. Li et al., A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities, CANCER RES, 60(4), 2000, pp. 873-876
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.