More frequent β-catenin gene mutations in adenomas than in aberrant crypt foci or adenocarcinomas in the large intestines of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-treated rats

Tetsuya Tsukamoto, Harunari Tanaka, Hiroko Fukami, Manami Inoue, Mami Takahashi, Keiji Wakabayashi, Masae Tatematsu

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24 Citations (Scopus)

Abstract

Alteration of adenomatous polyposis coli (APC) is known to be an early event in neoplasia, causing activation of the β-catenin/Tcf pathway. Although it is thought that alterations in APC and β-catenin may complement one another, the contribution of β-catenin mutations to colorectal carcinogenesis remains unclear. We therefore performed PCR-single strand conformation polymorphism analysis and direct sequencing of exon 3 of β-catenin gene in adenomas, adenocarcinomas, and aberrant crypt foci (ACF), considered to be putative precursor lesions of colorectal neoplasias, in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) treated F344 rats. β-Catenin mutations were identified in all of 7 adenomas (100%) and 6 of 12 (50%) adenocarcinomas. All of the mutations were found in codons 32 through 34, the serine encoded by codon 33 being an important phosphorylation site by glycogen synthase kinase-3β. Regarding ACF, 14 of 46 (30.4%) were found to be mutated, eleven (78%) in codon 34, and the others in codon 45 (frequently altered in human colon cancer), and codons 47 and 56 (which have not been previously reported). The frequency of β-catenin mutations in adenomas was significantly higher than in ACF (P<0.001) and adenocarcinomas (P<0.05). Thus, β-catenin mutations may have more importance in the genesis of adenomas than ACF or adenocarcinomas in rat colon carcinogens by PhIP.

Original languageEnglish
Pages (from-to)792-796
Number of pages5
JournalJapanese Journal of Cancer Research
Volume91
Issue number8
DOIs
Publication statusPublished - 01-01-2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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