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

• Published in: The American journal of pathology Vol. 158; no. 1; pp. 57 - 62
• Main Authors: Stemmer-Rachamimov, Anat O., Wiederhold, Thorsten, Nielsen, G. Petur, James, Marianne, Pinney-Michalowski, Denise, Roy, Jennifer E., Cohen, Wendy A., Ramesh, Vijaya, Louis, David N.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 2001; ASIP; American Society for Investigative Pathology
• Subjects: Adult; Biological and medical sciences; Blotting, Western; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line; Endometrium - chemistry; Epithelium - chemistry; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Mammary gland diseases; Medical sciences; Phosphoproteins - metabolism; Receptors, Estrogen - metabolism; Regular; Sodium-Hydrogen Exchangers; Tissue Distribution; Tumor Cells, Cultured; Tumors; Human; Immunohistochemistry; Carcinoma; Estrogen; Cell cell interaction; Malignant tumor; Carcinogenesis; Ovarian hormone; Pathology; Mammary gland diseases; Phosphoproteins; Female genital system; Mammary gland; Sex steroid hormone; Ion exchange; Endometrium; Hormonal receptor
• ISSN: 0002-9440; 1525-2191
• 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.