• BMB Reports
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• v.52 no.9
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• pp.548-553
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• 2019

Ets-1 is a prototype of the ETS protein family. Members of the ETS protein family contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. Many studies have shown a link between elevated expression of Ets-1 in cancer biopsies and poor survival. CCR7 is a chemokine that binds to specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. The objective of this study was to test whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data showed that CCR7 expression was downregulated in Ets-1-deficient T cells upon T-cell stimulation. Overexpression of Ets-1 increased CCR7 expression in breast cancer cell lines. In contrast, knockdown of Ets-1 reduced CCR7 expression. Ets-1 could directly bind to CCR7 promoter and mediate CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. Transactivation activity of Ets-1 was independent of the Pointed domain of Ets-1. Ets-1 could also enhance $NF-{\kappa}B$ and CBP transactivation of CCR7 promoter. Our results also showed that Ets-1 could modulate cancer cell transmigration by altering CCR7 expression in transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 can enhance CCR7 expression and contribute to tumor cell migration.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.29-37
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• 2003

Background: CC chemokine receptor (CCR) 7 and cognate CCR7 ligands, CCL21 (formerly secondary lymphoid tissue chemokine [SLC]) and CCL19 (formerly Epstein-Barr virus-induced molecule 1 ligand chemokine [ELC]), were known to establish microenvironment for the initiation of immune responses in secondary lymphoid tissue. As described previously, coadministration of DNA vaccine with CCR7 ligand-encoding plasmid DNA elicited enhanced humoral and cellular immunity via increasing the number of dendritic cells (DC) in secondary lymphoid tissue. The author hypothesized here that CCR7 ligand DNA could effectively expand memory CD4+ T cells to protect from viral infection likely via increasing DC number. Methods: To evaluate the effect of CCR7 ligand DNA on the expansion of memory CD4+ T cells, DO11.10.BALB/c transgenic (Tg)-mice, which have highly frequent ovalbumin $(OVA)_{323-339}$ peptide-specific CD4+ T cells, were used. Tg-mice were previously injected with CCR7 ligand DNA, then immunized with $OVA_{323-339}$ peptide plus complete Freund's adjuvant. Subsequently, memory CD4+ T cells in peripheral blood lymphocytes (PBL) were analyzed by FACS analysis for memory phenotype ($CD44^{high}$ and CD62 $L^{low}$) at memory stage. Memory CD4+ T cells recruited into inflammatory site induced with OVA-expressing virus were also analyzed. Finally, the protective efficacy against viral infection was evaluated. Results: CCR7 ligand DNA-treated Tg-mice showed more expanded $CD44^{high}$ memory CD4+ T cells in PBL than control vector-treated animals. The increased number of memory CD4+ T cells recruited into inflammatory site was also observed in CCR7 ligand DNA-treated Tg-mice. Such effectively expanded memory CD4+ T cell population increased the protective immunity against virulent viral infection. Conclusion: These results document that CCR7 and its cognate ligands play an important role in intracellular infection through establishing optimal memory T cell. Moreover, CCR7 ligand could be useful as modulator in DNA vaccination against viral infection as well as cancer.

• Journal of Life Science
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• v.13 no.4
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• pp.541-550
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• 2003

E2 glycoprotein of hepatitis C virus (HCV) comprises a surface of viral particle together with E1 glycoprotein, and is thought to be involved in the attachment of HCV viral particle to receptor (s) on the permissible cells including hepatocytes, B cells, T cells, and monocytes. We constructed a phage library expressing cellular proteins of hepatocytes on the phage surface, which turned out to be 8.8${\times}$$10^5$ cfu of diversity and carried inserts in 95% of library. We screened both cDNA phage library and 12-mer peptide library to identify the cellular proteins binding to E2 protein. Some intracellular proteins including tensin and membrane band 4.1 which are involved in signal transduction of survival and cytoskeleton organization, were selected from cDNA phage library through several rounds of panning and screening. On the contrary, membrane proteins such as CCR7, CKR-L2, and insulin-like growth factor-1 receptor were identified through screening of peptide library. Phages expressing peptides corresponding to those membrane proteins were bound to E2 protein specifically as determined by neutralization of binding assay. Since it is well known that HCV can infect T cells as well as hepatocytes, we examined to see if E2 protein can bind to CCR7, a member of C-protein coupled receptor family expressed on T cells, using CCR7 transfected tells. Human CCR7 cDNA was cloned into pcDNA3.1(-) vector and transfected into human embryonic kidney cell, 293T, and expressed on the surface of the cell as shown by flow cytometer. Binding assay of E2 protein using CCR7 transfected cells indicated that E2 protein bound to CCR7 by dose-dependent mode, giving rise to the possibility that CCR7 might be a putative cellular receptor for HCV.

• Journal of Integrative Natural Science
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• v.7 no.4
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• pp.234-240
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• 2014

C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

• IMMUNE NETWORK
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• v.2 no.2
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• pp.86-90
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• 2002

Background: Host genetic polymorphisms in the HIV-1 co-receptor CCR5 and CCR2b and SDF-1, ligand for co-receptor CXCR4, have been known to be associated with the resistance of HIV infection and/or the delayed disease progression in HIV-infected patients. Methods: We examined the frequencies of SDF1-3'A and CCR2b-64I alleles of 354 Koreans including 100 HIV-uninfected persons, 13 discordant spouses of HIV-infected persons, and 241 HIV-infected persons. The genotyping assays of SDF1 and CCR2b genes were carried out by polymerase chain reaction-restriction fragment length polymorphism. Results: The frequencies of CCR2b-64I and SDF1-3'A alleles in Koreans were very high compared with Caucasians and blacks. Observed frequencies of CCR2b-64I and SDF1-3'A allelic variants were 25.1% and 28.7%, respectively. The frequency of the CCR2b-64I allele in Koreans was 2~4 times higher than those of other ethnic groups with the exception of Asian. The frequencies of CCR2b-64I and SDF1-3'A genotypes did not show the significant difference between HIV-infected and uninfected Koreans. However, the prevalence of CCR2b-64I genotype of the LTNP group was about two times higher than that of the remainder group (P< 0.05). Four (45%) out of 9 LTNPs (long-term nonprogressors) showed having the SDF1-3'A allele and 7 (78%) out of 9 LTNPs carried the CCR2b-64I allele. 3 (33%) out of 9 LTNPs had both SDF1-3'A and CCR2b-64I alleles. But none of 5 RPs (rapid progressors) appeared to have both SDF1-3'A and CCR2b-64I alleles. Conclusion: The different genetic backgrounds in study populations may affect the disease progression and the AIDS epidemic in each country. Further studies need to define whether high frequencies of CCR2b-64I and SDF1-3'A allelic variants may affect the HIV disease progression.

• Journal of Navigation and Port Research
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• v.34 no.7
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• pp.577-585
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• 2010

This paper analyzes the efficiency of Korean Ship Component Part Manufacturer firms using DEA model. We evaluated the CCR, BCC efficiency and RTS of 30 Korea Ship Component Part Manufacturer firms. We also suggested the Korean Ship Component Part Manufacturer firms that can be benchmarked based on analyzed information. The result showed five enterprises whose values of CCR efficiency are 1, and eleven enterprises whose values of BCC efficiency are 1. RTS indicated IRS of 1 firms, DRS of 24 firms and CRS of 5 firms.

• The Journal of the Korea Contents Association
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• v.12 no.7
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• pp.284-294
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• 2012

In the study, we estimate efficiencies using CCR model of DEA, Super efficiency(AP) model, and super-SBM model with the data of 32 regional public hospitals in Korea from 205 to 2009. With Wilcoxon-Mann-Whitney statistics, we analyze efficiency differences for environmental factors(regions, type of hospital, type of operations, type of education training, relative importance of madicaids) among regional public hospitals. The results can be summarized as follows. Firstly, technical inefficiencies of regional public hospitals range from 15% to 17% in CCR model, 13% to 15% in AP model, 7% to 12.6% in SuperSBM model. Second, we confirm that environmental factors of hospitals cause different inefficiencies among them. The implication of this study is that policy and institutional change may need to improve the efficiencies along with internal managerial reform.

• The Journal of the Korea Contents Association
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• v.8 no.7
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• pp.201-207
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• 2008

The bankruptcy possibility of apartment construction firms has been incresed because of the environment of current apartment construction industry. This paper analyzes the efficiency of apartment construction firms using DEA model. We evaluate the CCR, BCC efficiency and RTS of 25 apartment construction firms. We also suggest the apartment construction firms which can be benchmarked based on analyzed information. The result shows that four enterprises whose values of CCR efficiency are 1, and ten enterprises whose values of BCC efficiency are 1. RTS indicates IRS of 21 firms and CRS of 4 firms.

• The Journal of the Korea Contents Association
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• v.10 no.11
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• pp.371-379
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• 2010

This study analyzes relative efficiency analysis for universities or colleges of Chung Cheong regions using data envelopment analysis. The main results of this study can by summarized as follows. First, in case of efficiency for CCR, the number of efficient universities(CCR value is one) are five universities. and mean value of CCR for universities located in Chungbuk region was most high. Second, the number of efficient colleges(CCR value is one) are three colleges. and mean value of CCR for colleges located in Daejeon region was most high. Third, in case of efficiency for BCC, the number of efficient universities(BCC value is one) are nine universities. and mean value of BCC for universities located in Chungbuk region was most high. Fourth, the number of efficient colleges(BCC value is one) are seven colleges. and mean value of BCC for colleges located in Chungbuk region was most high.

• Journal of Digital Convergence
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• v.10 no.9
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• pp.159-164
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• 2012

Although the display industry plays an important role in the entire Korean economy, few empirical research has analyzed the efficiency of display companies. The purpose of this paper is to measure and analyze efficiency of korean listed display firms using DEA(Data Envelopment Analysis) models. We evaluate the CCR and BCC efficiency in DEA models and the return to scale of the Korean listed display companies. The benchmarking companies and efficiency value for the display companies with inefficiency are also provided to improve their efficiency. We analyzed the 44 listed companies consisted of 7 listed on KOSPI and 37 listed on KOSDAQ at the end of 2010. The analysis results show six companies whose values of CCR are 1, and fourteen firms whose values of BCC efficiency are 1. In additions, the six companies have the scalability efficiency. Eventually the efficiency analysis can provide the valuable information for inefficient companies to find benchmarking companies and to improve their efficiency.