Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma

Abstract Background Protein tyrosine phosphatases (PTPs) regulate neuronal differentiation and survival, but their expression patterns and functions in human neuroblastoma (NB) are scarcely known. Here, we have investigated the function and expression of the non-receptor PTPN1 on human NB cell lines...

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Main Authors: Caroline E. Nunes-Xavier, Olaia Aurtenetxe, Laura Zaldumbide, Ricardo López-Almaraz, Asier Erramuzpe, Jesús M. Cortés, José I. López, Rafael Pulido
Format: Article
Language:English
Published: BMC 2019-12-01
Series:Diagnostic Pathology
Subjects:
Online Access:https://doi.org/10.1186/s13000-019-0919-9
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spelling doaj-036f5c9f8e934e5f8f7f6a6ce9b1d0572020-12-13T12:19:14ZengBMCDiagnostic Pathology1746-15962019-12-011411810.1186/s13000-019-0919-9Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastomaCaroline E. Nunes-Xavier0Olaia Aurtenetxe1Laura Zaldumbide2Ricardo López-Almaraz3Asier Erramuzpe4Jesús M. Cortés5José I. López6Rafael Pulido7Biomarkers in Cancer Unit, Biocruces Bizkaia Health Research InstituteBiomarkers in Cancer Unit, Biocruces Bizkaia Health Research InstituteDepartment of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU)Pediatric Oncology and Hematology, Cruces University HospitalQuantitative Biomedicine Unit, Biocruces Bizkaia Health Research InstituteQuantitative Biomedicine Unit, Biocruces Bizkaia Health Research InstituteBiomarkers in Cancer Unit, Biocruces Bizkaia Health Research InstituteBiomarkers in Cancer Unit, Biocruces Bizkaia Health Research InstituteAbstract Background Protein tyrosine phosphatases (PTPs) regulate neuronal differentiation and survival, but their expression patterns and functions in human neuroblastoma (NB) are scarcely known. Here, we have investigated the function and expression of the non-receptor PTPN1 on human NB cell lines and human NB tumor samples. Material/methods NB tumor samples from 44 patients were analysed by immunohistochemistry using specific antibodies against PTPN1, PTPRH, PTPRZ1, and PTEN. PTPN1 knock-down, cell proliferation and tyrosine phosphorylation analyses, and RT-qPCR mRNA expression was assessed on SH-SY5Y, SMS-KCNR, and IMR-32 human NB cell lines. Results Knock-down of PTPN1 in SH-SY5Y NB cells resulted in increased tyrosine phosphorylation and cell proliferation. Retinoic acid-mediated differentiation of NB cell lines did not affect PTPN1 mRNA expression, as compared with other PTPs. Importantly, PTPN1 displayed high expression on NB tumors in association with metastasis and poor prognosis. Conclusions Our results identify PTPN1 as a candidate regulator of NB cell growth and a potential NB prognostic biomarker.https://doi.org/10.1186/s13000-019-0919-9NeuroblastomaNeuroblastoma differentiationMetastatic neuroblastomaProtein tyrosine phosphatasesPTPN1
collection DOAJ
language English
format Article
sources DOAJ
author Caroline E. Nunes-Xavier
Olaia Aurtenetxe
Laura Zaldumbide
Ricardo López-Almaraz
Asier Erramuzpe
Jesús M. Cortés
José I. López
Rafael Pulido
spellingShingle Caroline E. Nunes-Xavier
Olaia Aurtenetxe
Laura Zaldumbide
Ricardo López-Almaraz
Asier Erramuzpe
Jesús M. Cortés
José I. López
Rafael Pulido
Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
Diagnostic Pathology
Neuroblastoma
Neuroblastoma differentiation
Metastatic neuroblastoma
Protein tyrosine phosphatases
PTPN1
author_facet Caroline E. Nunes-Xavier
Olaia Aurtenetxe
Laura Zaldumbide
Ricardo López-Almaraz
Asier Erramuzpe
Jesús M. Cortés
José I. López
Rafael Pulido
author_sort Caroline E. Nunes-Xavier
title Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
title_short Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
title_full Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
title_fullStr Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
title_full_unstemmed Protein tyrosine phosphatase PTPN1 modulates cell growth and associates with poor outcome in human neuroblastoma
title_sort protein tyrosine phosphatase ptpn1 modulates cell growth and associates with poor outcome in human neuroblastoma
publisher BMC
series Diagnostic Pathology
issn 1746-1596
publishDate 2019-12-01
description Abstract Background Protein tyrosine phosphatases (PTPs) regulate neuronal differentiation and survival, but their expression patterns and functions in human neuroblastoma (NB) are scarcely known. Here, we have investigated the function and expression of the non-receptor PTPN1 on human NB cell lines and human NB tumor samples. Material/methods NB tumor samples from 44 patients were analysed by immunohistochemistry using specific antibodies against PTPN1, PTPRH, PTPRZ1, and PTEN. PTPN1 knock-down, cell proliferation and tyrosine phosphorylation analyses, and RT-qPCR mRNA expression was assessed on SH-SY5Y, SMS-KCNR, and IMR-32 human NB cell lines. Results Knock-down of PTPN1 in SH-SY5Y NB cells resulted in increased tyrosine phosphorylation and cell proliferation. Retinoic acid-mediated differentiation of NB cell lines did not affect PTPN1 mRNA expression, as compared with other PTPs. Importantly, PTPN1 displayed high expression on NB tumors in association with metastasis and poor prognosis. Conclusions Our results identify PTPN1 as a candidate regulator of NB cell growth and a potential NB prognostic biomarker.
topic Neuroblastoma
Neuroblastoma differentiation
Metastatic neuroblastoma
Protein tyrosine phosphatases
PTPN1
url https://doi.org/10.1186/s13000-019-0919-9
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