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 ME RM proteins (merlin, ezrin, radixin and moesin) via its carboxyl terminus. Thus, NHE-RF may act as a multifunctional adaptor protein and play a role i n the assembly of signal transduction complexes, linking ion channels and r eceptors to the actin cytoskeleton, NHE-RF expression is up-regulated in re sponse to estrogen in estrogen receptor-positive breast carcinoma cell line s, suggesting that it may be involved in estrogen signaling. To further und erstand NHE-RF function and its possible role in estrogen signaling, we ana lyzed NHE-RF expression in normal human tissues, including cycling endometr ium, and in breast carcinomas, tissues in which estrogen plays an important role in regulating cell growth and proliferation. NHE-RF is expressed in m any epithelia, especially in cells specialized in ion transport or absorpti on, and is often localized to apical (luminal) membranes. NHE-RF expression varies markedly in proliferative versus secretory endometrium, with high e xpression 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 s ignaling.