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, 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.
Li
L C
LC
Department of Urology, Veterans Affairs Medical Center, and University of California San Francisco, 94121, USA.
Chui
R M
RM
Sasaki
M
M
Nakajima
K
K
Perinchery
G
G
Au
H C
HC
Nojima
D
D
Carroll
P
P
Dahiya
R
R
D000483:Alleles; D015820:Cadherins / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D015820:Cadherins; D009687:Nuclear Proteins