title: A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities.
abstract: E-cadherin plays a critical role in many aspects of cell adhesion, epithelial development, and the establishment and maintenance of epithelial polarity. The loss of the adhesive function of E-cadherin is a critical step in the promotion of epithelial cells to a more malignant phenotype. We identified a C/A single nucleotide polymorphism at -160 from the transcriptional start site of the E-cadherin gene promoter. Transient transfection experiments showed that the A allele of this polymorphism decreased the transcriptional efficiency by 68% compared with the C allele (P<0.001). Electrophoretic mobility shift and footprinting assays revealed that the C allele had a stronger transcriptional factor binding strength than the A allele. These results indicate that the -160 C/A polymorphism has a direct effect on E-cadherin gene transcriptional regulation. This allelic variation may be a potential genetic marker that can help identify those individuals at higher risk for invasive/metastatic diseases.
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, and University of California San Francisco, 94121, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Li
authors.forename: R M
authors.initials: RM
authors.lastname: Chui
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: G
authors.initials: G
authors.lastname: Perinchery
authors.forename: H C
authors.initials: HC
authors.lastname: Au
authors.forename: D
authors.initials: D
authors.lastname: Nojima
authors.forename: P
authors.initials: P
authors.lastname: Carroll
authors.forename: R
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000483:Alleles; D015820:Cadherins / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D015820:Cadherins; D009687:Nuclear Proteins