NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas.
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.
Stemmer-Rachamimov
A O
AO
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Wiederhold
T
T
Nielsen
G P
GP
James
M
M
Pinney-Michalowski
D
D
Roy
J E
JE
Cohen
W A
WA
Ramesh
V
V
Louis
D N
DN
D000328:Adult; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004717:Endometrium / Q000737:chemistry*; D004848:Epithelium / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010750:Phosphoproteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D010750:Phosphoproteins; D011960:Receptors, Estrogen; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor