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A dominant negative mutation of transforming growth factor-beta receptor type II gene in microsatellite stable oesophageal carcinoma.
Tanaka, S; Mori, M; Mafune, K; Ohno, S; Sugimachi, K.
Afiliación
  • Tanaka S; Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Br J Cancer ; 82(9): 1557-60, 2000 May.
Article en En | MEDLINE | ID: mdl-10789724
ABSTRACT
Recent investigations revealed microsatellite instability in colon cancers are associated with mutations of the transforming growth factor-beta receptor type II gene (TGF-beta RII) that encodes a transmembrane protein containing an intracellular serine/threonine kinase domain. Activation of TGF-beta receptor type I (RI) and RII by TGF-beta induces nuclear translocation of Smad proteins including Smad2 and Smad4 that have been originally identified as tumour suppressor genes. We have previously reported six cases with microsatellite instability in 32 oesophageal carcinomas. In this study, we analysed genetic mutations of TGF-beta RII, Smad2 and Smad4 in these oesophageal carcinoma tissues and established 16 cell lines. No genetic mutation was detected in any tissues or cell lines except one tissue sample of microsatellite stable oesophageal carcinoma, that is, a mis-sense mutation of glutamic acid to glutamine at codon 526 (E526Q) in the TGF-beta RII serine/threonine kinase domain. Interestingly, the mutant TGF-beta RII E526Q can completely inhibit TGF-beta-induction of nuclear translocation of Smad4 protein in oesophageal carcinoma cells. This mutation of TGF-beta RII that is not associated with microsatellite instability might make a dominant negative effect on TGF-beta signal transduction in oesophageal carcinoma.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Receptores de Factores de Crecimiento Transformadores beta / Repeticiones de Microsatélite / Genes Dominantes / Mutación Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Br J Cancer Año: 2000 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Receptores de Factores de Crecimiento Transformadores beta / Repeticiones de Microsatélite / Genes Dominantes / Mutación Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Br J Cancer Año: 2000 Tipo del documento: Article País de afiliación: Japón