Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 502, Issue 1-2, Pages 19-24Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0027-5107(02)00024-6
Keywords
E-cadherin; promoter; polymorphism; transcription; esophageal carcinoma; colorectal carcinoma
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E-cadherin is a tumor suppressor involved in epithelial cell-cell interactions. Some of the nucleotide variation in the 5'-promoter region of the gene influences transcriptional efficiency. We investigated single nucleotide polymorphisms (SNPs) in the promoter-exon 1 region of the E-cadherin gene (CDH1) using fluorescence-based PCR-single-strand conformation polymorphism (PCR-SSCP) analysis. We detected four kinds of polymorphisms between nucleotides -516 and + 12, numbering from the translation initiation site. SNPs were localized at -472G --> GA, -288T --> DeltaT -285C --> A, and -54G --> C. Variants -472GA and -285A were frequently found in controls. but the -288DeltaT and -54C are rare variants. We examined the effects of these variants on transcription. The activity of promoters containing the variants -288DeltaT, -285A, or -54C was lower than the activity of promoters with the major variants, as assayed by a luciferase reporter gene. Variants -472G and -472GA displayed the same promoter activity. The decreased transcriptional activity from variant promoters affects the expression of E-cadherin. (C) 2002 Elsevier Science B.V. All rights reserved.
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