Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins.
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...
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doaj-baf11ada3dda43aab3ca5486a6caa79c2021-03-04T00:21:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4431210.1371/journal.pone.0044312Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins.Paula A FerreiraRoberta R Ruela-de-SousaKarla C S QueirozAna Carolina S SouzaRenato MilaniRonaldo Aloise PilliMaikel P PeppelenboschJeroen den HertogCarmen V FerreiraThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22957062/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paula A Ferreira Roberta R Ruela-de-Sousa Karla C S Queiroz Ana Carolina S Souza Renato Milani Ronaldo Aloise Pilli Maikel P Peppelenbosch Jeroen den Hertog Carmen V Ferreira |
spellingShingle |
Paula A Ferreira Roberta R Ruela-de-Sousa Karla C S Queiroz Ana Carolina S Souza Renato Milani Ronaldo Aloise Pilli Maikel P Peppelenbosch Jeroen den Hertog Carmen V Ferreira Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins. PLoS ONE |
author_facet |
Paula A Ferreira Roberta R Ruela-de-Sousa Karla C S Queiroz Ana Carolina S Souza Renato Milani Ronaldo Aloise Pilli Maikel P Peppelenbosch Jeroen den Hertog Carmen V Ferreira |
author_sort |
Paula A Ferreira |
title |
Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins. |
title_short |
Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins. |
title_full |
Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins. |
title_fullStr |
Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins. |
title_full_unstemmed |
Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins. |
title_sort |
knocking down low molecular weight protein tyrosine phosphatase (lmw-ptp) reverts chemoresistance through inactivation of src and bcr-abl proteins. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
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. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22957062/?tool=EBI |
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