Different mutation status of the β-catenin gene in carcinogen-induced colon, brain, and oral tumors in rats

✍ Scribed by Masumi Suzui; Shigeyuki Sugie; Hideki Mori; Masataka Okuno; Takuji Tanaka; Hisataka Moriwaki

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 186 KB
• Volume: 32
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.10014

✦ Synopsis

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.