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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/baf11ada3dda43aab3ca5486a6caa79c
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spelling	oai:doaj.org-article:baf11ada3dda43aab3ca5486a6caa79c2021-11-18T07:06:33ZKnocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins.1932-620310.1371/journal.pone.0044312https://doaj.org/article/baf11ada3dda43aab3ca5486a6caa79c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22957062/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Paula A FerreiraRoberta R Ruela-de-SousaKarla C S QueirozAna Carolina S SouzaRenato MilaniRonaldo Aloise PilliMaikel P PeppelenboschJeroen den HertogCarmen V FerreiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44312 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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.
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.
format	article
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
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)
publishDate	2012
url	https://doaj.org/article/baf11ada3dda43aab3ca5486a6caa79c
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Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins.

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