Nuclear expression of NHERF1/EBP50 in Clear Cell Renal Cell Carcinoma.

The Na/H exchange regulatory factor 1 or Ezrin-radixin-moesin-binding phosphoprotein 50 (NHERF1/EBP50) is an adaptor protein implicated in the stabilization of molecular complexes linking extracellular signals with the cytoskeleton machinery. NHERF1 expression at the cell cortex is associated with the maintenance of adherent junction integrity in polarized epithelia. The role of NHERF1 in cancer depends on its localization within the cell, acting, in most cases, as a tumor suppressor when localized at the cell membrane, and as an oncogene, when expressed in the cytoplasm or the nucleus of cancer cells.

Bisphenol S increases EZRIN expression and the detrimental effects induced by dehydroepiandrosterone in rat endometrium.

The use of Bisphenol S (BPS) was proposed as an alternative to Bisphenol A (BPA), a chemical employed in the production of polycarbonate plastics and epoxy resins. BPA is a xenoestrogen that affects normal physiology in several species. It was reported that BPS may also act as a xenoestrogen with harmful effects in the reproductive system.

Similar expression pattern of NHERF1 and EZRIN in papillary but not in solid areas of human serous ovarian carcinomas.

NHERF1 is an adaptor protein expressed in the apical membrane of polarized epithelia, which interacts with the EZRIN-Radixin-Moesin (ERM) family of proteins connecting signaling pathways to the cell cytoskeleton. NHERF1 and EZRIN cooperate in the maintenance of the apical microvilli in polarized epithelial cells. In several types of cancers, NHERF1 and EZRIN are displaced from the apical compartment to the cytoplasm and nuclei of cancer cells.

A novel splicing mutation in the SLC9A3R1 gene in tumors from ovarian cancer patients.

The aim of the present study was to investigate novel molecular markers that could improve the diagnosis of ovarian cancer patients or be of predictive value. The sequence of the sodium-hydrogen antiporter 3 regulator 1 (SLC9A3R1) gene that codes for the PDZ2 motif of the Na/H exchanger regulatory factor 1 (NHERF1) protein was analyzed. Changes in migration and cell transformation, and alterations of growth factor signaling pathways have been described in cells lacking endogenous NHERF1 or expressing an isoform lacking the function of the PDZ2 domain.

Subcellular redistribution of NHERF1 in response to dehydroepiandrosterone (DHEA) administration in endometrial glands of Wistar rats.

To understand the regulation of Na(+)/H(+) exchanger regulatory factor (NHERF1) in polycystic ovarian syndrome, we studied the expression of NHERF1 in uterus of Wistar rats injected with (6 mg/kg) of dehydroepiandrosterone (DHEA) for 7 and 20 days. Immunohistochemistry analysis of NHERF1 showed a substantial shift in the intracellular localization of NHERF1 in endometrial glands and areas of luminal epithelium as early as 7 days of DHEA administration. The NHERF1 accumulated in the "Golgi apparatus area" virtually in all the glands in the 7-day protocol, and in the majority of the glands of 20-day protocol.

Expression of NHERF1 in colonic tumors induced by 1,2-dimethylhydrazine in rats is independent of plasma ovarian steroids.

In normal embryonic fibroblasts, the Na(+)/H(+) exchanger regulator factor 1 (NHERF1) stabilizes E-cadherin/β-catenin binding and the lack of NHERF1 expression promotes cell transformation thus acting as a tumor suppressor gene. We here tested the hypothesis that NHERF1 could act as a tumor suppressor gene in colon cancer as a mediator of estrogens' protective actions in colon carcinogenesis. We studied the expression and localization of NHERF1 and β-catenin by immunohistochemistry in colonic tumors induced by 1,2 dimethylhidrazine (DMH) in Sprague-Dawley rats.

Estrogens regulate the expression of NHERF1 in normal colon during the reproductive cycle of Wistar rats.

In breast cancer cell lines, the Na(+)/H(+) exchanger regulator factor 1 (NHERF1) gene is regulated at the transcriptional level by estrogens, the protein expression levels correlate with the presence of estrogen receptors and the effect is blocked by anti-estrogens. However, there is limited information regarding the regulation of NHERF1 by estrogens in normal colon tissue. The NHERF1 protein has an important role in the maintenance of the intestine ultrastructure.

Therapeutic effect of boron neutron capture therapy (BNCT) on field cancerized tissue: inhibition of DNA synthesis and lag in the development of second primary tumors in precancerous tissue around treated tumors in DMBA-induced carcinogenesis in the hamster cheek pouch oral cancer model.

Objective: We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue.

Homogeneous boron targeting of heterogeneous tumors for boron neutron capture therapy (BNCT): chemical analyses in the hamster cheek pouch oral cancer model.

Objective: BNCT is a tumour cell targeted radiation therapy. Uniform targeting of heterogeneous tumours with therapeutically effective boron carriers would contribute to a therapeutic effect on all tumour cell populations and avoid radioresistant fractions. This remains an unresolved challenge.

PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling.

PTEN, a tumor suppressor frequently inactivated in many human cancers, directly antagonizes the activity of phosphatidylinositol-3-OH kinase (PI3K) by dephosphorylating phosphoinositides. We show here that PTEN interacts directly with the NHERF1 and NHERF2 (Na+/H+ exchanger regulatory factor) homologous adaptor proteins through the PDZ motif of PTEN and the PDZ1 domain of NHERF1 or both PDZ domains of NHERF2. NHERFs were shown to interact directly with platelet-derived growth factor receptor (PDGFR), and we demonstrate the assembly of a ternary complex between PTEN, NHERFs and PDGFR.

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 organizes ERM proteins at the apical membrane of polarized epithelia.

Ezrin-radixin-moesin (ERM) proteins regulate the organization and function of specific cortical structures in polarized epithelial cells by connecting filamentous (F)-actin to plasma membrane proteins. The contribution of ERM proteins to these structures depends on a conformational change to an active state in which the C-terminal region interacts with F-actin and the N-terminal domain interacts with membrane ligands. The specific ligands necessary for stabilizing ERM proteins at the membrane are not known.

Biodistribution of GB-10 (Na(2)(10)B10H10 compound for boron neutron capture therapy (BNCT) in an experimental model of oral cancer in the hamster cheek pouch.

Objective: We previously proposed the hamster cheek pouch model of oral cancer for BNCT studies. We herein present the biodistribution of a non-toxic boron compound, GB-10 (Na(2)(10)B10H10), in this model to assess its potential for BNCT or BNCT enhanced Fast Neutron Therapy.

Materials And Methods: We evaluated the uptake and retention of GB-10 in tumour and precancerous tissue and in potentially dose-limiting, clinically relevant normal tissues.

Prostate cancer cells-osteoblast interaction shifts expression of growth/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts.

Purpose: Prostate cancer specifically metastasizes to bone where it leads to bone formation. We previously reported that coculturing MDA PCa 2b prostate cancer cells with primary mouse osteoblasts (PMOs) induced PMO proliferation and differentiation. An osteoblastic reaction was also observed in vivo after injection of MDA PCa 2b cells into the bones of severe combined immunodeficient disease mice.

Biodistribution of a carborane-containing porphyrin as a targeting agent for Boron Neutron Capture Therapy of oral cancer in the hamster cheek pouch.

Boron Neutron Capture Therapy (BNCT) is a bimodal cancer treatment based on the selective accumulation of 10B in tumors and concurrent irradiation with thermalized neutrons. The short-range, high-LET radiation produced by the capture of neutrons by 10B could potentially control tumor while sparing normal tissue if the boron compound targets tumor selectively within the treatment volume. In previous studies, we proposed and validated the hamster cheek pouch model of oral cancer for BNCT studies, proved that absolute and relative uptake of the clinically employed boron compound boronophenylalanine (BPA) would be potentially therapeutic in this model and provided evidence of the efficacy of in vivo BPA-mediated BNCT to control hamster oral mucosa tumors with virtually no damage to normal tissue.