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Type: Artigo de periódico
Title: Knocking Down Low Molecular Weight Protein Tyrosine Phosphatase (lmw-ptp) Reverts Chemoresistance Through Inactivation Of Src And Bcr-abl Proteins.
Author: Ferreira, Paula A
Ruela-de-Sousa, Roberta R
Queiroz, Karla C S
Souza, Ana Carolina S
Milani, Renato
Pilli, Ronaldo Aloise
Peppelenbosch, Maikel P
den Hertog, Jeroen
Ferreira, Carmen V
Abstract: The development of multidrug resistance (MDR) limits the efficacy of continuous chemotherapeutic treatment in chronic myelogenous leukemia (CML). Low molecular weight protein tyrosine phosphatase (LMW-PTP) is up-regulated in several cancers and has been associated to poor prognosis. This prompted us to investigate the involvement of LMW-PTP in MDR. In this study, we investigated the role of LMW-PTP in a chemoresistant CML cell line, Lucena-1. Our results showed that LMW-PTP is highly expressed and 7-fold more active in Lucena-1 cells compared to K562 cells, the non-resistant cell line. Knocking down LMW-PTP in Lucena-1 cells reverted chemoresistance to vincristine and imatinib mesylate, followed by a decrease of Src and Bcr-Abl phosphorylation at the activating sites, inactivating both kinases. On the other hand, overexpression of LMW-PTP in K562 cells led to chemoresistance to vincristine. Our findings describe, for the first time, that LMW-PTP cooperates with MDR phenotype, at least in part, through maintaining Src and Bcr-Abl kinases in more active statuses. These findings suggest that inhibition of LMW-PTP may be a useful strategy for the development of therapies for multidrug resistant CML.
Subject: Antineoplastic Agents
Caspase 3
Cell Line, Tumor
Cell Survival
Drug Resistance, Neoplasm
Fusion Proteins, Bcr-abl
Gene Expression Regulation, Leukemic
K562 Cells
Molecular Weight
Protein Tyrosine Phosphatases
Src-family Kinases
Citation: Plos One. v. 7, n. 9, p. e44312, 2012.
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0044312
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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