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[Cancer Research 60, 873-876, February 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

A Single Nucleotide Polymorphism in the E-cadherin Gene Promoter Alters Transcriptional Activities1

Long-Cheng Li, Richard M. Chui, Masahiro Sasaki, Koichi Nakajima, Geetha Perinchery, Harry C. Au, Dana Nojima, Peter Carroll and Rajvir Dahiya2

Department of Urology, Veterans Affairs Medical Center, and University of California San Francisco, San Francisco, California 94121

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.




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