Biological role of NHERF1 protein expression in breast cancer

Histopathology. 2009 Nov;55(5):600-8. doi: 10.1111/j.1365-2559.2009.03424.x.


Aims: To determine the role of Na+/H+ exchanger regulatory factor (NHERF1) in breast cancerogenesis and progression.

Methods and results: NHERF1 expression was examined in normal tissue, ductal carcinoma in situ (DCIS), invasive carcinoma (IBC), synchronous metastatic lymph node and metachronous distant metastases of a retrospective series of breast cancers. Fifty-one IBC, 42 DCIS and normal tissues were examined immunohistochemically, and the colocalization between NHERF1 and HER2/neu was studied by immunofluorescence. NHERF1 showed a different localization and pattern of expression in the different compartments of the breast. The mean value of cytoplasmic NHERF1 expression in paired samples was significantly higher in DCIS, IBC, distant metastases and metastatic lymph nodes with respect to normal tissues. Moreover, in metastatic lymph nodes NHERF1 was exclusively cytoplasmic. In the membrane NHERF1 was colocalized with overexpressed HER2/neu in DCIS, IBC and distant metastases.

Conclusions: Breast cancerogenesis is characterized by increased cytoplasmic expression of NHERF1 as the tumour progresses, suggesting a role in this process. The switch from apical membranous to cytoplasmic expression is compatible with a dual role for NHERF1 as a tumour suppressor or tumour promoter dependent on its subcellular localization.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma in Situ / metabolism*
  • Carcinoma in Situ / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Neoplasm Staging
  • Phosphoproteins / biosynthesis*
  • Receptor, ErbB-2 / biosynthesis
  • Sodium-Hydrogen Exchangers / biosynthesis*


  • Biomarkers, Tumor
  • Phosphoproteins
  • Sodium-Hydrogen Exchangers
  • sodium-hydrogen exchanger regulatory factor
  • Receptor, ErbB-2