Frequent mutations of the rat β-catenin gene in colon cancers induced by methylazoxymethanol acetate plus 1-hydroxyanthraquinone

✍ Scribed by Masumi Suzui; Toshikazu Ushijima; Roderick H. Dashwood; Naoki Yoshimi; Takashi Sugimura; Hideki Mori; Minako Nagao

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 172 KB
• Volume: 24
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199903)24:3<232::aid-mc10>3.0.co;2-m

✦ Synopsis

Recent evidence suggests that the β-catenin gene (CTNNB1) acts as an oncogene, and some human colon tumors with an intact APC gene have activating mutations in CTNNB1. In this study, mutations in the region corresponding to N-terminal phosphorylation sites (codons 1-51) of the rat Ctnnb1 gene were investigated in 20 colon tumors associated with ulcerative colitis and induced with methylazoxymethanol acetate and 1hydroxyanthraquinone. Ninety percent (18 of 20) of the tumors induced in male F344 rats harbored mutations, which were detected in three of four adenomas (75%) and 15 of 16 adenocarcinomas (94%). Of 18 total missense mutations, 13 (72%) were G→A transitions at position 101, three were G→A transitions at position 94, and two were C→T transitions at position 122, resulting in the amino acid substitutions Gly 34 →Glu, Asp 32 →Asn, and Thr 41 →Ile, respectively. Although there were no mutations in the Apc gene, as we previously reported in the same tumor samples, the results obtained in this study strongly implicate the Apc-β-catenin-T-cell factor (Tcf) signaling pathway in methylazoxymethanol acetate, 1-hydroxyanthraquinone-induced colon carcinogenesis.