| http://purl.uniprot.org/citations/22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22532587 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutation of K-Ras is a frequent oncogenic event in human cancers, particularly cancers of lungs, pancreas, and colon. It remains unclear why some tissues are more susceptible to Ras-induced transformation than others. Here, we globally activated a mutant oncogenic K-Ras allele (K-Ras(G12D)) in mice and examined the tissue-specific effects of this activation on cancer pathobiology, Ras signaling, tumor suppressor, DNA damage, and inflammatory responses. Within 5 to 6 weeks of oncogenic Ras activation, mice develop oral and gastric papillomas, lung adenomas, and hematopoietic hyperproliferation and turn moribund. The oral, gastric, and lung premalignant lesions display activated extracellular signal-regulated kinases (Erk)1/2 and NF-κB signaling as well as activated tumor suppressor and DNA damage responses. Other organs such as pancreas, liver, and small intestine do not exhibit neoplastic progression within 6 weeks following K-Ras(G12D) activation and do not show a potent tumor suppressor response. Even though robust Erk1/2 signaling is activated in all the tissues examined, the pErk1/2 distribution remains largely cytoplasmic in K-Ras(G12D)-refractory tissues (pancreas, liver, and intestines) as opposed to a predominantly nuclear localization in K-Ras(G12D)-induced neoplasms of lung, oral, and gastric mucosa. The downstream targets of Ras signaling, pElk-1 and c-Myc, are elevated in K-Ras(G12D)-induced neoplastic lesions but not in K-Ras(G12D)-refractory tissues. We propose that oncogenic K-Ras-refractory tissues delay oncogenic progression by spatially limiting the efficacy of Ras/Raf/Erk1/2 signaling, whereas K-Ras-responsive tissues exhibit activated Ras/Raf/Erk1/2 signaling, rapidly form premalignant tumors, and activate potent antitumor responses that effectively prevent further malignant progression."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.org/dc/terms/identifier | "doi:10.1158/1541-7786.mcr-12-0089"xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/author | "Nguyen T.A."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/author | "Donehower L.A."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/author | "Herron A."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/author | "Parikh N."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/author | "Shuck R.L."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/name | "Mol Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/pages | "845-855"xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/title | "Mouse tissues that undergo neoplastic progression after K-Ras activation are distinguished by nuclear translocation of phospho-Erk1/2 and robust tumor suppressor responses."xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/22532587 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22532587 |
| http://purl.uniprot.org/citations/22532587 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SV36-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SVY1-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A0N4SWH5-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_P63085-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_Q0VDV7-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A338P736-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A338P781-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RPX4-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RPZ0-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |
| http://purl.uniprot.org/uniprot/#_B2KGV5-mappedCitation-22532587 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22532587 |