ArticleMolecular carcinogenesis2015
Genetic analysis of colon tumors induced by a dietary carcinogen PhIP in CYP1A humanized mice: Identification of mutation of β-catenin/Ctnnb1 as the driver gene for the carcinogenesis.
Article in Molecular carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Tissue Organoid Cultures Metabolize Dietary Carcinogens Proficiently and Are Effective Models for DNA Adduct Formation.Chemical research in toxicology · 2024Article
- Review
- The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy.Biomarker research · 2021Review
- Colitis-induced IL11 promotes colon carcinogenesis.Carcinogenesis · 2021Article
- Major challenges in accurate mutation detection of multifocal lung adenocarcinoma by next-generation sequencing.Cancer biology & therapy · 2020Article
- Multi-Omics Integration Reveals a Competitive Endogenous RNAs Network for the Identification of Progression Biomarkers and the Stratification of Patients Diagnosed With Nephroblastoma.Frontiers in oncology · 2020Article
- Genetic alterations in Japanese extrahepatic biliary tract cancer.Oncology letters · 2017Article
- Divergent roles of p120-catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen-induced rat skin tumors.Molecular carcinogenesis · 2017Article
- From the Cover: PhIP/DSS-Induced Colon Carcinogenesis in CYP1A-Humanized Mice and the Possible Role of Lgr5+ Stem Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.Molecular carcinogenesis · 2017Article
- Obesity promotes PhIP-induced small intestinal carcinogenesis in hCYP1A-db/db mice: involvement of mutations and DNA hypermethylation of Apc.Carcinogenesis · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Replacing mouse Cyp1a with human CYP1A enables the humanized CYP1A mice to mimic human metabolism of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), by N(2) -hydroxylation to a proximate carcinogen. Our previous study demonstrated that PhIP, combined with the dextrin sulfate sodium (DSS)-induced colitis, induces colon carcinogenesis in hCYP1A mice. Here, we employed whole exome sequencing and found multiple gene mutations in PhIP/DSS-induced colon tumors. Mutations in the exon 3 of Ctnnb1/β-catenin, however, were the predominant events. We further sequenced the key fragments of Apc, Ctnnb1, and Kras, because mutations of these genes in the humans are commonly found as the drivers of colorectal cancer. Mutations on either codon 32 or 34 in the exon 3 of Ctnnb1 were found in 39 out of 42 tumors, but no mutation was found in either Apc or Kras. The sequence context of codons 32 and 34 suggests that PhIP targets +3G in a TGGA motif of Ctnnb1. Since mutations that activate Wnt signal is a major driving force for human colorectal cancers, we conclude that the mutated β-catenin is the driver in PhIP/DSS-induced colon carcinogenesis. This result suggests that the colon tumors in hCYP1A mice mimic human colorectal carcinogenesis not only in the dietary etiology involving PhIP, but also in the aberrant activation of the Wnt signaling pathway as the driving force.
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