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(American Journal of Pathology. 2001;158:57-62.)
© 2001 American Society for Investigative Pathology

Regular Articles

NHE-RF, a Merlin-Interacting Protein, Is Primarily Expressed in Luminal Epithelia, Proliferative Endometrium, and Estrogen Receptor-Positive Breast Carcinomas

Anat O. Stemmer-Rachamimov*, Thorsten Wiederhold{dagger}, G. Petur Nielsen*, Marianne James{dagger}, Denise Pinney-Michalowski{dagger}, Jennifer E. Roy*, Wendy A. Cohen*, Vijaya Ramesh{dagger} and David N. Louis*

From the Molecular Neuro-Oncology Laboratory*
and Molecular Neurogenetics Unit,{dagger}
Departments of Pathology, Neurosurgery, Neurology and Genetics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

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.




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