ArticleOncogene2007
Conditional expression of mutated K-ras accelerates intestinal tumorigenesis in Msh2-deficient mice.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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.
Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Colorectal cancer murine models: Initiation to metastasis.Cancer letters · 2024Review
- Combinatorial Network of Transcriptional and miRNA Regulation in Colorectal Cancer.International journal of molecular sciences · 2023Article
- Mouse models of colorectal cancer: Past, present and future perspectives.World journal of gastroenterology · 2020Review
- Review
- Inducible Intestine-Specific Expression of krasNeoplasia (New York, N.Y.) · 2018Article
- ANIMAL MODELS FOR COLORECTAL CANCER.Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery · 2018Review
- Mouse model of proximal colon-specific tumorigenesis driven by microsatellite instability-induced Cre-mediated inactivation of Apc and activation of Kras.Journal of gastroenterology · 2016Article
- Mouse models of DNA mismatch repair in cancer research.DNA repair · 2016Review
- DNA mismatch repair deficiency accelerates lung neoplasm development in K-ras(LA1/+) mice: a brief report.Cancer medicine · 2015Article
- Application of a novel regulatable Cre recombinase system to define the role of liver and gut metabolism in drug oral bioavailability.The Biochemical journal · 2015Article
- Animal models of gastrointestinal and liver diseases. New mouse models for studying dietary prevention of colorectal cancer.American journal of physiology. Gastrointestinal and liver physiology · 2014Review
- Wild-type K-ras has a tumour suppressor effect on carcinogen-induced murine colorectal adenoma formation.International journal of experimental pathology · 2014Article
- Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion.EMBO reports · 2014Article
- Animal models of colorectal cancer.Cancer metastasis reviews · 2013Review
- Genomic instability and colon carcinogenesis: from the perspective of genes.Frontiers in oncology · 2013Article
- First case report of turcot syndrome type 1 in Colombia.Case reports in oncological medicine · 2012Article
- Homeobox gene Rhox5 is regulated by epigenetic mechanisms in cancer and stem cells and promotes cancer growth.Molecular cancer · 2011Article
- Acute sensitivity of the oral mucosa to oncogenic K-ras.The Journal of pathology · 2011Article
- Activation of K-RAS by co-mutation of codons 19 and 20 is transforming.Journal of molecular signaling · 2011Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
K-ras mutation occurs in 40-50% of human colorectal adenomas and carcinomas, but its contribution to intestinal tumorigenesis in vivo is unclear. We developed K-ras(V12) transgenic mice that were crossed with Ah-Cre mice to generate K-ras(V12)/Cre mice, which showed beta-naphthoflavone-induction of Cre-mediated LoxP recombination that activated intestinal expression of K-ras(V12) 4A and 4B transcripts and proteins. Only very occasional intestinal adenomas were observed in beta-naphthoflavone-treated K-ras(V12)/Cre mice aged up to 2 years, suggesting that mutated K-ras expression alone does not significantly initiate intestinal tumourigenesis. To investigate the effects of mutated K-ras on DNA mismatch repair (MMR)-deficient intestinal tumour formation, these mice were crossed with Msh2(-/-) mice to generate K-ras(V12)/Cre/Msh2(-/-) offspring. After beta-naphthoflavone treatment, K-ras(V12)/Cre/Msh2(-/-) mice showed reduced average lifespan of 17.3+/-5.0 weeks from 26.9+/-6.8 (control Msh2(-/-) mice) (P<0.01). They demonstrated increased adenomas in the small intestine from 1.41 (Msh2(-/-) controls) to 7.75 per mouse (increased fivefold, P<0.01). In the large intestine, very few adenomas were found in Msh2(-/-) mice (0.13 per mouse) whereas K-ras(V12)/Cre/Msh2(-/-) mice produced 2.70 adenomas per mouse (increased 20-fold, P<0.01). Over 80% adenomas from K-ras(V12)/Cre/Msh2(-/-) mice showed transgene recombination with expression of K-ras(V12) 4A and 4B transcripts and proteins. Sequencing of endogenous murine K-ras showed mutations in two out of 10 tumours examined from Msh2(-/-) mice, but no mutations in 17 tumours from K-ras(V12)/Cre/Msh2(-/-) mice. Expression of K-ras(V12) in tumours caused activation of the mitogen-activated protein kinase and Akt/protein kinase B signaling pathways, demonstrated by phosphorylation of p44MAPK, Akt and GSK3beta, as well as transcriptional upregulation of Pem, Tcl-1 and Trap1a genes (known targets of K-ras(V12) expression in stem cells). Thus, mutated K-ras cooperates synergistically with MMR deficiency to accelerate intestinal tumorigenesis, particularly in the large intestine.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.