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The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene

Neuregulin-1 (NRG1) is both a candidate oncogene and candidate tumour suppressor gene. It encodes the heregulins and other mitogenic ligands for the ERBB family, but it also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression...

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Autores principales: Chua, YL, Ito, Y, Pole, JCM, Newman, S, Chin, S-F, Stein, RC, Ellis, IO, Caldas, C, O’Hare, MJ, Murrell, A, Edwards, PAW
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789334/
https://www.ncbi.nlm.nih.gov/pubmed/19802002
http://dx.doi.org/10.1038/onc.2009.259
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author Chua, YL
Ito, Y
Pole, JCM
Newman, S
Chin, S-F
Stein, RC
Ellis, IO
Caldas, C
O’Hare, MJ
Murrell, A
Edwards, PAW
author_facet Chua, YL
Ito, Y
Pole, JCM
Newman, S
Chin, S-F
Stein, RC
Ellis, IO
Caldas, C
O’Hare, MJ
Murrell, A
Edwards, PAW
author_sort Chua, YL
collection PubMed
description Neuregulin-1 (NRG1) is both a candidate oncogene and candidate tumour suppressor gene. It encodes the heregulins and other mitogenic ligands for the ERBB family, but it also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression of NRG1. This included cell lines that had translocation breaks in the gene. Similarly, expression in cancers was generally comparable to or less than various normal breast samples. Many non-expressing cell lines had extensive methylation of the CpG island at the principal transcription start site at exon 2 of NRG1. Expression was reactivated by demethylation. Many tumours also showed methylation, while normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. siRNA-mediated depletion of NRG1 increased net proliferation, in a normal breast cell line and a breast cancer cell line that expressed NRG1. The short arm of chromosome 8 is frequently lost in epithelial cancers, and NRG1 is the most centromeric gene that is always affected. NRG1 may therefore be the major tumour suppressor gene postulated to be on 8p: it is in the correct location, is anti-proliferative, and is silenced in many breast cancers.
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spelling pubmed-27893342010-05-19 The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene Chua, YL Ito, Y Pole, JCM Newman, S Chin, S-F Stein, RC Ellis, IO Caldas, C O’Hare, MJ Murrell, A Edwards, PAW Oncogene Article Neuregulin-1 (NRG1) is both a candidate oncogene and candidate tumour suppressor gene. It encodes the heregulins and other mitogenic ligands for the ERBB family, but it also causes apoptosis in NRG1-expressing cells. We found that most breast cancer cell lines had reduced or undetectable expression of NRG1. This included cell lines that had translocation breaks in the gene. Similarly, expression in cancers was generally comparable to or less than various normal breast samples. Many non-expressing cell lines had extensive methylation of the CpG island at the principal transcription start site at exon 2 of NRG1. Expression was reactivated by demethylation. Many tumours also showed methylation, while normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. siRNA-mediated depletion of NRG1 increased net proliferation, in a normal breast cell line and a breast cancer cell line that expressed NRG1. The short arm of chromosome 8 is frequently lost in epithelial cancers, and NRG1 is the most centromeric gene that is always affected. NRG1 may therefore be the major tumour suppressor gene postulated to be on 8p: it is in the correct location, is anti-proliferative, and is silenced in many breast cancers. 2009-10-05 2009-11-19 /pmc/articles/PMC2789334/ /pubmed/19802002 http://dx.doi.org/10.1038/onc.2009.259 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chua, YL
Ito, Y
Pole, JCM
Newman, S
Chin, S-F
Stein, RC
Ellis, IO
Caldas, C
O’Hare, MJ
Murrell, A
Edwards, PAW
The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
title The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
title_full The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
title_fullStr The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
title_full_unstemmed The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
title_short The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
title_sort nrg1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789334/
https://www.ncbi.nlm.nih.gov/pubmed/19802002
http://dx.doi.org/10.1038/onc.2009.259
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