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

Y. L. Chua, Y. Ito, J. C.M. Pole, S. Newman, S. F. Chin, R. C. Stein, I. O. Ellis, C. Caldas, M. J. O'Hare, A. Murrell, P. A.W. Edwards

Research output: Contribution to journalArticlepeer-review

60 Citations (SciVal)

Abstract

Neuregulin-1 (NRG1) is both a candidate oncogene and a candidate tumour suppressor gene. It not only encodes the heregulins and other mitogenic ligands for the ERBB family, but 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 that in 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, whereas normal mammary epithelial fragments had none. Lower NRG1 expression correlated with higher methylation. Small interfering RNA (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 antiproliferative and is silenced in many breast cancers.

Original languageEnglish
Pages (from-to)4041-4052
Number of pages12
JournalOncogene
Volume28
Issue number46
DOIs
Publication statusPublished - 5 Oct 2009

Bibliographical note

Funding Information:
We thank Huai-En Huang for some exploratory expression analysis. This study was funded principally by the Breast Cancer Campaign and also by Cancer Research UK, Hutchison-Whampoa Ltd. (who endowed the buildings in which the work was done) and the Ludwig Institute for Cancer Research.

Keywords

  • Breast cancer
  • Chromosome rearrangement
  • DNA methylation
  • Heregulins
  • NRG1
  • Tumour suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint

Dive into the research topics of 'The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene'. Together they form a unique fingerprint.

Cite this