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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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 |
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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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