東邦大学 教育・研究業績データベース   
     


  アリタ ミチツネ   Arita Michitsune
  有田 通恒
   所属   東邦大学  医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 A single nucleotide substitution (-107C→ G) in hMLH1 promoter found in colorectal cancer population reduces transcriptional activity
掲載誌名 正式名:Biochemical genetics
略  称:Biochem Genet
ISSNコード:00062928
巻・号・頁 45(9-10),671-681頁
著者・共著者 Zhong X, Arita M, Yamada K, Sugiyama H, Tan K, Kanazawa S, Koike J, Teramoto T, Hemmi, H
発行年月 2007/10
概要 Inactivation of the DNA mismatch repair gene hMLH1 predisposes one to colorectal cancer. We have identified a C to G nucleotide substitution at position -107 relative to the hMLH1 gene translation initiation site in three of 163 colorectal cancer patients with an allele frequency of 0.0092 (3/326). One of the three -107G alleles occurred in one patient out of five with reduced hMLH1 expression in the tumor tissue. The -107G was not found in 63 healthy individuals. This substitution reduced transcriptional activity by 51% compared with -107C (P<0.01) and impeded the promoter-binding capacity of nuclear proteins. Although the small number of identified -107G alleles is insufficient to evaluate the contribution to the carcinogenesis and clinicopathological properties of the tumors, the effects of -107G on hMLH1 gene transcription and nuclear protein binding to the promoter sequence implicate the site, including -107C, as a crucial element interacting with the activator that maintains hMLH1 gene expression.
文献番号 PMID: 17690979