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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titleKnockdown of insulin receptor substrate 1 reduces proliferation and downregulates Akt/mTOR and MAPK pathways in K562 cellspt_BR
dc.contributor.authorMachado-Neto, JApt_BR
dc.contributor.authorFavaro, Ppt_BR
dc.contributor.authorLazarini, Mpt_BR
dc.contributor.authorCosta, FFpt_BR
dc.contributor.authorSaad, STOpt_BR
dc.contributor.authorTraina, Fpt_BR
unicamp.author.emailfabiolat@unicamp.brpt_BR
unicamp.authorMachado-Neto, Joao Agostinho Favaro, Patricia Lazarini, Mariana Costa, Fernando Ferreira Saad, Sara T. Olalla Traina, Fabiola Univ Estadual Campinas, Hematol & Hemotherapy Ctr, UNICAMP, Hemoctr,Inst Nacl Ciencia & Tecnol Sangue, BR-13083878 Campinas, SP, Brazilpt_BR
unicamp.authorFavaro, Patricia Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo, Brazilpt_BR
dc.subjectIRS1pt_BR
dc.subjectAkt/mTORpt_BR
dc.subjectMAPKpt_BR
dc.subjectK562 cellpt_BR
dc.subjectBCR-ABLpt_BR
dc.subjectProliferationpt_BR
dc.subject.wosChronic Myeloid-leukemiapt_BR
dc.subject.wosPhiladelphia-chromosomept_BR
dc.subject.wosSignaling Pathwayspt_BR
dc.subject.wosGene-expressionpt_BR
dc.subject.wosPhosphoinositide 3-kinasept_BR
dc.subject.wosP110-delta Isoformpt_BR
dc.subject.wosTyrosine Kinasept_BR
dc.subject.wosCancer Cellspt_BR
dc.subject.wosIrs-1pt_BR
dc.subject.wosOverexpressionpt_BR
dc.description.abstractBCR-ABL kinase activates downstream signaling pathways, including the PI3K-Akt/mTOR and the MAPK pathway. IRS1 has been previously described as constitutively phosphorylated and associated with BCR-ABL in K562 cells, suggesting that IRS1 has role in the BCR-ABL signaling pathways. In this study, we analyzed the effect of IRS1 silencing, by shRNA-lentiviral delivery, in K562 cells, a CML cell line that presents the BCR-ABL. IRS1 silencing decreased cell proliferation and colony formation in K562 cells, which correlates with the delay of these cells at the G0/G1 phase and a decrease in the S phase of the cell cycle. Furthermore, IRS1 silencing in K562 cells resulted in a decrease of Akt, P70S6K and ERK1/2 phosphorylation. Nevertheless, apoptosis was unaffected by IRS1 knockdown and no alterations were found in the phosphorylation of BAD and in the expression of BCL2 and BAX. BCR-ABL and CRKL phosphorylation levels remained unaffected upon IRS1 silencing, and no synergistic effect was observed with imatinib treatment and IRS1 knockdown, indicating that IRS1 is downstream from BCR-ABL In conclusion, we demonstrated that inhibition of IRS1 is capable of inducing the downregulation of Akt/mTOR and MAPK pathways and further decreasing proliferation, and clonogenicity and induces to cell cycle delay at G0/G1 phase in BCR-ABL cells. (C) 2011 Elsevier B.V. All rights reserved.pt
dc.relation.ispartofBiochimica Et Biophysica Acta-molecular Cell Researchpt_BR
dc.relation.ispartofabbreviationBiochim. Biophys. Acta-Mol. Cell Res.pt_BR
dc.publisher.cityAmsterdampt_BR
dc.publisher.countryHolandapt_BR
dc.publisherElsevier Science Bvpt_BR
dc.date.issued2011pt_BR
dc.date.monthofcirculationAUGpt_BR
dc.identifier.citationBiochimica Et Biophysica Acta-molecular Cell Research. Elsevier Science Bv, v. 1813, n. 8, n. 1404, n. 1411, 2011.pt_BR
dc.language.isoenpt_BR
dc.description.volume1813pt_BR
dc.description.issuenumber8pt_BR
dc.description.firstpage1404pt_BR
dc.description.lastpage1411pt_BR
dc.rightsfechadopt_BR
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policypt_BR
dc.sourceWeb of Sciencept_BR
dc.identifier.issn0167-4889pt_BR
dc.identifier.wosidWOS:000292945200002pt_BR
dc.identifier.doi10.1016/j.bbamcr.2011.04.002pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.date.available2014-07-30T14:35:57Z
dc.date.available2015-11-26T17:13:21Z-
dc.date.accessioned2014-07-30T14:35:57Z
dc.date.accessioned2015-11-26T17:13:21Z-
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dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/61021
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/61021-
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