Ezrin, a membrane cytoskeleton linking protein, is a member of ezrin/radixin/moesin (ERM) that regulates cell shape, motility and cell to cell interaction via linking the contractile elements of the cell to transmembrane proteins. Ezrin, through this mechanism, has been thought to play an important role in cancer progression and distant metastasis. In addition, high levels of ezrin expression have been noted in many cancers, such as breast, colon, osteosarcoma, and prostate cancer. Gynecologic cancer cells, with high levels of ezrin expression, have more invasive potential than that of the lower levels of ezrin expressed cancer cells. High levels of ezrin expression are also related to the advanced histological grade and poor outcome. Recently, several reports have also demonstrated that ezrin expression is enhanced and almost localized at the membranous portion in high stage tumor cells and metastatic gynecologic cancer cells. Therefore, in the near future, ezrin levels and its cellular location might serve as essential markers for the metastasis of gynecologic cancers.
Breast ; Cell Communication ; Cell Shape ; Colon ; Cytoskeletal Proteins ; Cytoskeleton ; Membranes ; Neoplasm Metastasis ; Osteosarcoma ; Prostatic Neoplasms ; Proteins

OBJECTIVE: To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG). METHODS: For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene. RESULTS: Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis. CONCLUSION Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.
Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Mutation

PURPOSE: Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma. MATERIALS AND METHODS: Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens. RESULTS: Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (> or =90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036). CONCLUSION: The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.
Cytoskeletal Proteins ; Humans ; Korea ; Membranes ; Neoplasm Metastasis ; Osteoblasts ; Osteosarcoma ; Recurrence ; Retrospective Studies ; Stress, Psychological

Background: Since recent reports showed the possibility that cytoskeletal proteins, which were known to be exclusively within the cytoplasm, might play a role in the re-distribution of the intranuclear chromatin in a certain type of the cells under specific circumstances, we tried to show a change in the intracellular distribution of microtubule protein in artificially induced senescent PC12 pheochromocytoma cells. Methods: PC12 pheochromocytoma cells (ATCC CRL-1721) were grown in the culture media including 1 micrometer 3'-Azido-3'-deoxythymidine (AZT, Sigma-Aldrich, USA). The senescence of the cells was confirmed by senescence detection kit (Calbiochem, San Diego, CA). Immunocytochemical study was also performed in the cells treated with AZT during 0, 75 and 153 days. Results: beta-tubuline was not observed in the cells not treated with AZT. The same protein was localized within the nuclei in the senescent cells treated with AZT during 153 days. Conclusion: Microtubule might be involved in some crucial roles in the redistribution of chromatin within the nuclei of the senescent cells.
Aging ; Animals ; Cell Aging ; Chromatin ; Culture Media ; Cytoplasm ; Cytoskeletal Proteins ; Microtubules* ; PC12 Cells* ; Pheochromocytoma ; Tubulin ; Zidovudine

BACKGROUND: Ezrin, a member of the ezrin-radixin-moesin family, is implicated in tumor progression, metastatic dissemination, and adverse outcomes, in several cancer types. In this study, we explored the clinicopathological significance of ezrin expression in non-small cell lung carcinomas (NSCLCs). METHODS: Immunohistochemical analysis of tissue microarray with 112 surgically resected NSCLC specimens, was performed to examine the ezrin expression. We also correlated ezrin expression with other clinicopathological features and prognosis. RESULTS: The ezrin-positive group revealed significantly higher correlation with pleural invasion (p=0.016) and pathologic stage (p=0.050). Univariate survival analysis showed that ezrin-positive group had a significantly shorter cancer-specific survival than ezrin-negative group (p=0.016). Meanwhile, female (p=0.030), no pleural invasion (p=0.023), no lymphatic invasion (p=0.026), and early pathologic stage (p=0.008) significantly correlated with longer survival. Multivariate survival analysis showed that variables such as ezrin positivity (p=0.032), female (p=0.035), and early pathologic stage (p=0.001) were independent prognostic factors for NSCLC. CONCLUSIONS: Ezrin might be a molecular marker to predict poor prognosis of NSCLC.
Carcinoma, Non-Small-Cell Lung ; Cytoskeletal Proteins ; Female ; Humans ; Lung ; Prognosis

BACKGROUND: Distinction of dermatofibroma (DF) from dermatofibrosarcoma protuberans (DFSP) is occasionally difficult. Histologically, DF shows fibrohistiocyte growth, and DFSP shows myofibroblast proliferation. This difference is usually targeted by several immunohistochemical staining to differentiate between these two entities. Ezrin, a member of ezrin-radixin-moesin family of protein, has a critical role in oncogenic transformation. And endothelin-1 (ET-1) is a family of endothelin-derived peptides that promotes myofibroblast contraction and migration. OBJECTIVE: The purpose of this study was to evaluate the usefulness of ezrin and endothelin-1 in differentiating between DF and DFSP. METHODS: Formalin-fixed and paraffin-embedded tissues from 20 DFs and 10 DFSPs were immunohistochemically stained with ezrin and ET-1 monoclonal antibodies. RESULTS: No DF case showed ezrin expression, whereas 3 of 10 DFSP cases showed weak positive reaction for ezrin. This difference was not statistically significant. In DF, 5 cases showed strong positive, 3 showed moderate positive, 4 were weak positive and 8 cases showed negative by ET-1 staining. In DFSP, 6 cases were strong positive, 1 was moderate positive, 2 were weak positive and 1 showed negative by ET-1. CONCLUSION: Ezrin and endothelin-1 are not useful in distinguishing between DF and DFSP. Further studies are needed to determine the factors which differentiate DFSP from DF.
Antibodies, Monoclonal ; Contracts ; Cytoskeletal Proteins ; Dermatofibrosarcoma ; Endothelin-1 ; Histiocytoma, Benign Fibrous ; Humans ; Myofibroblasts ; Peptides

OBJECTIVETo investigate the expression of corticosteroids and regional expression 16 (CR16) in the testis of patients with idiopathic azoospermia and the role of CR16 in spermatogenesis.

METHODSImmunohistochemistry and RT-PCR were used to detect the expression levels of the CR16 protein and mRNA in the testes of 48 patients with idiopathic azoospermia and 10 healthy men.

RESULTSImmunohistochemistry showed that the CR16 protein expressed in the Sertoli cells and spermatids-binding region in the epithelium of seminiferous tubules. The level of the CR16 protein was markedly lower in the idiopathic azoospermia patients than in the healthy men, and RT-PCR also showed a significantly decreased level of CR16 mRNA in the testis of the patients.

CONCLUSIONThe expressions of the CR16 protein and mRNA decrease markedly in the testis of patients with idiopathic azoospermia, indicating a correlation with the pathogenesis of azoospermia.

Adult ; Azoospermia ; metabolism ; pathology ; Case-Control Studies ; Cytoskeletal Proteins ; metabolism ; Humans ; Male ; Testis ; metabolism ; pathology

OBJECTIVETo examine the distributions of beta-catenin and adenomatous polyposis coli (APC) protein in the tooth germ, and obtain the messages of function of the two factors and the relationship between them.

METHODSMice were selected and cohabited with the ratio of female mice to male ones being 2:1, and Embryo day 0.5 was confirmed based on the finding of vaginal plug. The distributions of beta-catenin and APC protein in the Embryos on day 13.5, 14.5, 15.5, 16.5, 17.5 were examined in the paraffin-embedded sections by immunohistochemistry methods.

RESULTSDuring E13.5 d to E17.5 d, positive expression of beta-catenin was found in the oral epithelium and the dental lamina, and became more and more strong. The staining were whole cell. During the bud stage, strong positive expression of APC protein was found in the oral epithelium and the dental lamina, but the expression displayed a down-regulation tendency. The staining was the cytomembrane and cytoplasm. There was negative correlation between beta-catenin and APC protein (P<0.01).

CONCLUSIONThe result of beta-catenin suggests its contribution in the early development of enamel organ and the proliferation of cell. Coincidance of the two factors staining site was found, according to the statistics.

Adenomatous Polyposis Coli Protein ; Animals ; Cytoskeletal Proteins ; Female ; Immunohistochemistry ; Male ; Mice ; Tooth Germ ; beta Catenin

Cytoskeletal Proteins ; biosynthesis ; genetics ; physiology ; Humans ; Neoplasm Metastasis ; Neoplasms ; pathology ; Signal Transduction

Animals ; Cytoskeletal Proteins ; biosynthesis ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Hepatocytes ; metabolism ; ultrastructure ; Rats ; Rats, Sprague-Dawley