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http://repositorio.unicamp.br/jspui/handle/REPOSIP/348429
Type: | Artigo |
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: | Proteína tirosina fosfatase |
Country: | Estados Unidos |
Editor: | Public Library of Science |
Rights: | Aberto |
Identifier DOI: | 10.1371/journal.pone.0044312 |
Address: | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0044312 |
Date Issue: | 2012 |
Appears in Collections: | IQ - Artigos e Outros Documentos IB - Artigos e Outros Documentos |
Files in This Item:
File | Description | Size | Format | |
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000308463800055.pdf | 429.1 kB | Adobe PDF | View/Open |
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