Evidence map›Paper›PMID 25131582›Full record

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.

Hong Wang, Hong Zhou, Anna Liu, Xiangyi Guo, Chung S Yang

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. 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 · 2017
    Article
  10. Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Hong WangSusan L. Cullman Laboratory for Cancer Research, Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Hong ZhouDepartment of Mathematics, University of Saint Joseph, West Hartford, Connecticut.
Anna LiuSusan L. Cullman Laboratory for Cancer Research, Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Xiangyi GuoSusan L. Cullman Laboratory for Cancer Research, Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Chung S YangSusan L. Cullman Laboratory for Cancer Research, Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Rutgers, The State University of New Jersey · USUniversity of Saint Joseph · US

Funding

TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Tracie Saunders · 1997 to 2026
$94.5M
Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI PANOS G. GEORGOPOULOS · 1988 to 2026
$47.4M
Prevention of Colon Cancer by Epigallocatechin Gallate and AtorvastatinR01CA120915 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI YANG, CHUNG S. · 2007 to 2011
$1.8M
Mechanistic Studies on Lung Cancer Prevention by Tea PolyphenolsR01CA122474 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI YANG, CHUNG S. · 2008 to 2012
$1.6M
Inhibition of Lung Carcinogenesis by Tea Polyphenols and AtorvastatinR01CA133021 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI YANG, CHUNG S. · 2008 to 2012
$1.6M
NCI NIH HHS CA72720NCI NIH HHS P30 CA072720NCI NIH HHS R01 CA120915NCI NIH HHS R01CA120915NCI NIH HHS R01 CA122474NCI NIH HHS R01 CA133021NIEHS NIH HHS ES05022NIEHS NIH HHS P30 ES005022
6 · The paper itself

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.

Indexed as

Animalsbeta CateninCarcinogenesisCarcinogensColonic NeoplasmsCytochrome P-450 CYP1A1DietExonsFemaleGenes, APCGenes, rasHumansImidazolesMaleMiceMutation2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridinebeta CateninCarcinogensCTNNB1 protein, mouseCYP1A1 protein, humanCytochrome P-450 CYP1A1Imidazolescarcinogenesiscolorectal cancerdriver mutationexon sequencing

Identifiers

PMID25131582
PMCPMC4331268
OpenAlexW2155380042

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.