ArticleProceedings of the National Academy of Sciences of the United States of America2010
Tissue-specific p19Arf regulation dictates the response to oncogenic K-ras.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
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- Roles of ARF tumour suppressor protein in lung cancer: time to hit the nail on the head!Molecular and cellular biochemistry · 2021Review
- Generation of an Fsp1 (fibroblast-specific protein 1)-Flpo transgenic mouse strain.Genesis (New York, N.Y. : 2000) · 2020Article
- Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer.JCI insight · 2019Article
- Testis-specific Arf promoter expression in a transposase-aided BAC transgenic mouse model.Molecular biology reports · 2019Article
- A model for RAS mutation patterns in cancers: finding the sweet spot.Nature reviews. Cancer · 2018Review
- H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression.Nature communications · 2018Article
- Autochthonous murine models for the study of smoker and never-smoker associated lung cancers.Translational lung cancer research · 2018Review
- HP1γ Promotes Lung Adenocarcinoma by Downregulating the Transcription-Repressive Regulators NCOR2 and ZBTB7A.Cancer research · 2018Article
- GATA3 zinc finger 2 mutations reprogram the breast cancer transcriptional network.Nature communications · 2018Article
- Article
- p53 loss does not permit escape from BrafOncogene · 2017Article
- Tissue-specific tumorigenesis: context matters.Nature reviews. Cancer · 2017Review
- Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer.Molecular cancer · 2017Review
- Article
- Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers.Nature communications · 2016Article
- An extra copy ofJCI insight · 2016Article
- Cell type-specific properties and environment shape tissue specificity of cancer genes.Scientific reports · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
The ability of oncogenes to engage tumor suppressor pathways represents a key regulatory mechanism that can limit the outgrowth of incipient tumor cells. For example, in a number of settings oncogenic Ras strongly activates the Ink4a/Arf locus, resulting in cell cycle arrest or senescence. The capacity of different cell types to execute tumor suppressor programs following expression of endogenous K-ras(G12D) in vivo has not been examined. Using compound mutant mice containing the Arf(GFP) reporter and the spontaneously activating K-ras(LA2) allele, we have uncovered dramatic tissue specificity of K-ras(G12D)-dependent p19(Arf) up-regulation. Lung tumors, which can arise in the presence of functional p19(Arf), rarely display p19(Arf) induction. In contrast, sarcomas always show robust activation, which correlates with genetic evidence, suggesting that loss of the p19(Arf)-p53 pathway is a requisite event for sarcomagenesis. Using constitutive and inducible RNAi systems in vivo, we highlight cell type-specific chromatin regulation of Ink4a/Arf as a critical determinant of cellular responses to oncogenic K-ras. Polycomb-group complexes repress the locus in lung tumors, whereas the SWI/SNF family member Snf5 acts as an important mediator of p19(Arf) induction in sarcomas. This variation in tumor suppressor induction might explain the inherent differences between tissues in their sensitivity to Ras-mediated transformation.
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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.