Journal Article

Frequent mutations of the β-<i>catenin</i> gene in mouse colon tumors induced by azoxymethane

Mami Takahashi, Seiichi Nakatsugi, Takashi Sugimura and Keiji Wakabayashi

in Carcinogenesis

Volume 21, issue 6, pages 1117-1120
Published in print June 2000 | ISSN: 0143-3334
Published online June 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.6.1117
Frequent mutations of the β-catenin gene in mouse colon tumors induced by azoxymethane

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The β-catenin gene is frequently mutated at codons 33, 41 and 45 of the glycogen synthase kinase-3β phosphorylation motif in human colon cancers in patients without APC mutations. Frequent mutations at codons 32 and 34, as well as 33 and 41, have been detected in rat colon tumors induced by azoxymethane (AOM), with the second G of CTGGA sequences being considered as a mutational hot-spot. In the present study, exon 3 of the β-catenin gene in mouse colon tumors induced by AOM was amplified by PCR and mutations were detected by the single strand conformation polymorphism method, restriction enzyme fragment length polymorphism and direct sequencing. All 10 colon tumors tested were found to have β-catenin mutations, four in codon 34, three in codon 33, two in codon 41 and one in codon 37, nine being G:C→A:T transitions. However, no mutations were found in codon 32 of the mouse β-catenin gene. On immmunostaining, β-catenin was observed in the cytoplasm and nucleus of the tumor cells. The cytoplasmic staining was homogeneous, while both homogeneous and heterogeneous patterns were noted for the nuclei. Highly frequent mutations of the β-catenin gene in AOM-induced mouse colon tumors suggest that consequent alterations in the stability and localization of the protein may play an important role in this colon carcinogenesis model.

Keywords: AOM, azoxymethane; DMH, 1,2-dimethylhydrazine; GSK-3β, glycogen synthase kinase-3β; RFLP, restriction enzyme fragment length polymorphism; SSCP, single strand conformation polymorphism; Tcf, T cell factor.

Journal Article.  2660 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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