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Different mutation status of the β‐catenin gene in carcinogen‐induced colon, brain, and oral tumors in rats
Author(s) -
Suzui Masumi,
Sugie Shigeyuki,
Mori Hideki,
Okuno Masataka,
Tanaka Takuji,
Moriwaki Hisataka
Publication year - 2001
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10014
Subject(s) - biology , carcinogenesis , microbiology and biotechnology , gene , gene mutation , mutation , carcinogen , single strand conformation polymorphism , adenocarcinoma , cancer research , transversion , genetics , cancer
Abstract Mutations in the region corresponding to the N‐terminal phosphorylation sites (codons 1–51) of the rat β‐catenin gene (Ctnnb1) were investigated in rat colon tumors induced by 1‐hydroxyanthraquinone (1‐HA) plus methylazoxymethanol (MAM) acetate, by using polymerase chain reaction (PCR)–single‐strand conformation polymorphism (SSCP) analysis. The β‐catenin gene was also screened for mutations in rat brain and oral tumors induced by ethyl nitrosourea (ENU) and 4‐nitroquinoline 1‐oxide (4‐NQO), respectively. In colon tumors, β‐catenin gene mutations were found in two of three adenomas (67%) and 26 of 28 adenocarcinomas (93%), with a total incidence of 90% (28 of 31 adenomas plus adenocarcinomas). Eight (29%) were 34 G→T (second position), eight (29%) were 32 G→A (first position), five (18%) were 34 G→A (first position), five (18%) were 41 C→T (second position), one (4%) was 34 G→A (second position), and one (4%) was 32 A→G (second position), mutations, resulting in the substitutions of Gly 34 →Val, Asp 32 →Asn, Gly 34 →Arg, Thr 41 →Ile, Gly 34 →Glu, and Asp 32 →Gly, respectively. The 34 G→T (second position) mutations found in this study were unique compared to those found in other carcinogen‐induced rat colon carcinogenesis models. In contrast, β‐catenin gene mutations were not found in either the brain or oral tumors. These results suggest that mutations in the β‐catenin gene in rat tumors occur in specific tissues or organ sites and in a carcinogen‐specific manner. Thus, the mutation spectrum in the β‐catenin gene is organ‐ and chemical carcinogen‐specific. © 2001 Wiley‐Liss, Inc.

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