Breast Cancer Research and Treatment

, Volume 96, Issue 2, pp 163–168 | Cite as

Neuregulins 1–4 are expressed in the cytoplasm or nuclei of ductal carcinoma (in situ) of the human breast

  • Catherine Marshall
  • Edith Blackburn
  • Mellissa Clark
  • Steven Humphreys
  • William J. Gullick
Preclinical study


A new family of epidermal growth factor-like proteins, the Neuregulins (NRGs), have recently been identified and are expressed in a range of normal tissues and in some forms of cancer including breast cancer. In this study we examined using immunohistochemical staining expression of NRG1alpha, NRG1beta, NRG2alpha, NRG2beta, NRG3 and NRG4 in sixty cases of pre-invasive ductal carcinoma in situ of the breast representing different degrees of differentiation. Each protein was expressed in a high proportion of these cases showing a predominantly homogenous cytoplasmic staining pattern. Nuclear expression of NRG1alpha, NRG1beta, and NRG3 was however also observed in a significant fraction of cases. High levels of expression of NRG2beta and NRG4 were associated with high-grade tumours (p≤0.005), NRG2beta staining was associated with tumour size >25 mm (p=0.005) while NRG3 nuclear staining was present more often in low-grade tumours (p=0.039). This data demonstrates that each member of the NRG family of ligands is present in pre-invasive ductal breast cancer and that they may be involved in regulating cell behaviour. The significance of intranuclear expression remains to be determined but suggests a novel mechanism of action for some of these proteins.


breast cancer ductal carcinoma growth factor heregulin neuregulin 


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Edith Blackburn is supported by a grant from the E B Hutchinson Trust. Mellissa Clark is a recipient of a Postgraduate Studentship from the Biotechnology and Biosciences Research Council.


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Copyright information

© Springer 2005

Authors and Affiliations

  • Catherine Marshall
    • 1
  • Edith Blackburn
    • 2
  • Mellissa Clark
    • 2
  • Steven Humphreys
    • 1
  • William J. Gullick
    • 2
    • 3
  1. 1.Preston Hall Hospital Maidstone, Aylesford, KentUK
  2. 2.Department of Biosciences, Cancer Biology LaboratoryUniversity of KentCanterbury, KentUK
  3. 3.Department of Biosciences, Cancer Biology LaboratoryUniversity of KentCanterbury, KentUK

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