{"data":{"id":"10.6084/m9.figshare.1571360","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1571360","prefix":"10.6084","suffix":"m9.figshare.1571360","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Steinmetz, Birgit","nameType":"Personal","givenName":"Birgit","familyName":"Steinmetz","affiliation":[],"nameIdentifiers":[]},{"name":"Hackl, Hubert","nameType":"Personal","givenName":"Hubert","familyName":"Hackl","affiliation":[],"nameIdentifiers":[]},{"name":"Schwarzinger, Ilse","nameType":"Personal","givenName":"Ilse","familyName":"Schwarzinger","affiliation":[],"nameIdentifiers":[]},{"name":"Spittler, Andreas","nameType":"Personal","givenName":"Andreas","familyName":"Spittler","affiliation":[],"nameIdentifiers":[]},{"name":"Wieser, Rotraud","nameType":"Personal","givenName":"Rotraud","familyName":"Wieser","affiliation":[],"nameIdentifiers":[]},{"name":"Slabáková, Eva","nameType":"Personal","givenName":"Eva","familyName":"Slabáková","affiliation":[],"nameIdentifiers":[]},{"name":"Smějová, Monika","nameType":"Personal","givenName":"Monika","familyName":"Smějová","affiliation":[],"nameIdentifiers":[]},{"name":"Arbesu, Itziar","nameType":"Personal","givenName":"Itziar","familyName":"Arbesu","affiliation":[],"nameIdentifiers":[]},{"name":"Medhat Shehata","affiliation":[],"nameIdentifiers":[]},{"name":"Souček, Karel","nameType":"Personal","givenName":"Karel","familyName":"Souček","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"The oncogene \u003ci\u003eEVI1\u003c/i\u003e enhances transcriptional and biological responses of human myeloid cells to \u003ci\u003eall-trans\u003c/i\u003e retinoic acid"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2014,"subjects":[{"subject":"110309 Infectious Diseases","subjectScheme":"FOR"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Hematology"},{"subject":"111714 Mental Health","subjectScheme":"FOR"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Biological Sciences"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Chemistry"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"}],"contributors":[],"dates":[{"date":"2015-10-09","dateType":"Created"},{"date":"2015-10-09","dateType":"Updated"},{"date":"2014","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.4161/15384101.2014.946869","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1755105 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"The product of the \u003ci\u003ee\u003c/i\u003ecotropic \u003ci\u003ev\u003c/i\u003eirus \u003ci\u003ei\u003c/i\u003entegration site 1 (\u003ci\u003eEVI1\u003c/i\u003e) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, \u003ci\u003eall-trans\u003c/i\u003e retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the \u003ci\u003eRAR\u003c/i\u003eβ gene, but repressed the ATRA induction of the \u003ci\u003eEVI1\u003c/i\u003e gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing \u003ci\u003eEVI1\u003c/i\u003e through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for \u003ci\u003eGDF15\u003c/i\u003e, which codes for a member of the TGF-β superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of \u003ci\u003eGDF15\u003c/i\u003e counteracted some of these effects. The potential clinical implications of these findings are discussed.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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