NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas

Am J Pathol. 2001 Jan;158(1):57-62. doi: 10.1016/S0002-9440(10)63944-2.


NHE-RF, a regulatory cofactor for NHE (Na(+)-H(+) exchanger) type 3, interacts with ion transporters and receptors through its PDZ domains and with the MERM proteins (merlin, ezrin, radixin and moesin) via its carboxyl terminus. Thus, NHE-RF may act as a multifunctional adaptor protein and play a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin cytoskeleton. NHE-RF expression is up-regulated in response to estrogen in estrogen receptor-positive breast carcinoma cell lines, suggesting that it may be involved in estrogen signaling. To further understand NHE-RF function and its possible role in estrogen signaling, we analyzed NHE-RF expression in normal human tissues, including cycling endometrium, and in breast carcinomas, tissues in which estrogen plays an important role in regulating cell growth and proliferation. NHE-RF is expressed in many epithelia, especially in cells specialized in ion transport or absorption, and is often localized to apical (luminal) membranes. NHE-RF expression varies markedly in proliferative versus secretory endometrium, with high expression in proliferative (estrogen-stimulated) endometrium. Furthermore, estrogen receptor status and NHE-RF expression correlate closely in breast carcinoma specimens. These findings support a role for NHE-RF in estrogen signaling.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Endometrium / chemistry*
  • Epithelium / chemistry*
  • Female
  • Humans
  • Immunohistochemistry
  • Phosphoproteins / metabolism*
  • Receptors, Estrogen / metabolism*
  • Sodium-Hydrogen Exchangers
  • Tissue Distribution
  • Tumor Cells, Cultured


  • Phosphoproteins
  • Receptors, Estrogen
  • Sodium-Hydrogen Exchangers
  • sodium-hydrogen exchanger regulatory factor