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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.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.subjectK562 cellpt_BR
dc.subject.wosChronic Myeloid-leukemiapt_BR
dc.subject.wosSignaling Pathwayspt_BR
dc.subject.wosPhosphoinositide 3-kinasept_BR
dc.subject.wosP110-delta Isoformpt_BR
dc.subject.wosTyrosine Kinasept_BR
dc.subject.wosCancer Cellspt_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
dc.relation.ispartofBiochimica Et Biophysica Acta-molecular Cell Researchpt_BR
dc.relation.ispartofabbreviationBiochim. Biophys. Acta-Mol. Cell Res.pt_BR
dc.publisherElsevier Science Bvpt_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.sourceWeb of Sciencept_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.description.provenanceMade available in DSpace on 2014-07-30T14:35:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2011en
dc.description.provenanceMade available in DSpace on 2015-11-26T17:13:21Z (GMT). No. of bitstreams: 2 WOS000292945200002.pdf: 939542 bytes, checksum: 24dbe9655d570c449f9275d2c156d0d8 (MD5) WOS000292945200002.pdf.txt: 42801 bytes, checksum: f74acd3ead95b1f8a8dbcc1c57cc49a1 (MD5) Previous issue date: 2011en
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