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ABSTRACT: In urban areas, the quantity of exhaust particles from vehicle emissions is tremendous and has been regarded as the main contributor
to particulate matter (PM) pollution. Recently, the nano-sized PM on public health has begun to raise the attention. The increased
toxicity of nanoparticulate can be largely explained by their small size, high airborne concentration, extensive surface area
and high content of organic carbon and transition metals. We have attempted to address the toxicity of nano sized-particlulate
matter by comparing various particulates including micro-SiO2 (mSiO2), nano-SiO2 (nSiO2), micro-TiO2 (mTiO2), and nano-TiO2 (nTiO2) in RAW264.7 cells and invivo. The cell viability of all particulates decreased dose dependently. 24-h incubation with nSiO2
demonstrated apoptosis in RAW264.7 using Annexin-V binding immunofluorescent microscopy, but not in any other particulates.
Invivo, cytotoxicity of nanosized was higher than micro-sized particulates. As higher the concentration of particulates,
the more pulmonary injury and neutrophilic infiltration were observed in nano-sized than micro-sized particulates, respectively.
Particularly, 5.0mg/kg of mTiO2 never shows any increase of neutrophile even with high cellularity of total cells and macrophages. From these results, we
suggested that particulate-induced respiratory toxicity be influenced by component, size, and dose of particulates including
the characteristic nature of the target cells invitro and invivo.
Journal of Nanoparticle Research 04/2012; 11(1):55-65. · 3.29 Impact Factor
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ABSTRACT: Abstract
Background
Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.
Methods
DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.
Results
Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).
Conclusion
Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.
World Journal of Surgical Oncology. 01/2010;
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ABSTRACT: Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.
DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.
Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).
Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.
World Journal of Surgical Oncology 01/2010; 8:32. · 1.12 Impact Factor
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ABSTRACT: Emphysema is the major component of chronic obstructive pulmonary disease (COPD), which is the fourth leading cause of death in the world. Several epidemiologic studies suggest that genetic factors may have an important role in the pathogenesis of emphysema. We analyzed the gene expression profiles of chromosomal aberrations using array comparative genomic hybridization (array CGH) in 32 patients with emphysema to identify the candidate genes that might be causally involved in the pathogenesis of emphysema. Copy number gains and losses were detected in chromosomal regions, and the corresponding genes were confirmed by real-time polymerase chain reaction. Several frequently altered loci were found, including a gain at 5p15.33 (60% of the study subjects), and a loss at 7q22.1 (31% of the study subjects). DNA gains were identified at a high frequency at 1p, 5p, 11p, 12p, 15q, 17p, 18q, 21q, and 22q, whereas DNA losses were frequently found at 7q and 22q. We found that the fold change levels were highest at the CYP4B1 (1p33), JUN (1p32.1), NOTCH2 (1p12-p11.2), SDHA (5p15.33), KCNQ1 (11p15.5-p15.4), NINJ2 (12p13.33), PCSK6 (15q26.3), ABR (17p13.3), CTDP1 (18q23), RUNX1 (21q22.12) and HDAC10 (22q13.33) gene loci. We also observed losses in the MUC17 (7q22.1), COMT (22q11.21) and GSTT1 (22q11.2) genes. These studies show that array CGH is a useful tool for the identification of gene alterations in cases of emphysema and that the aforementioned genes might represent potential candidate genes involved in the pathogenesis of emphysema.
Beiträge zur Klinik der Tuberkulose 05/2009; 187(3):165-72. · 1.90 Impact Factor
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ABSTRACT: To investigate the incidence and the risk factors for occult ipsilateral or contralateral central neck lymph node (LN)metastasis in patients with unilateral papillary thyroid carcinoma (PTC) and a clinically negative neck.
Elective central lymph node dissection (CLND) in patients with PTC remains controversial. There have been few prospective studies assessing accurate histopathologic information and predictive factors for the presence of metastasis to the ipsilateral or contralateral central compartment of the neck in patients with PTC and clinically negative neck nodes.
We reviewed a prospective protocol of 111 unilateral PTC patients with clinically node-negative necks who have received total thyroidectomy and elective bilateral CLND from 2005 to 2007. The relationships between LN metastasis to the ipsilateral or contralateral central neck compartment and clinico-pathologic factors such as age, sex, size of primary tumor, perithyroidal invasion, lymphovascular invasion, and capsular invasion were analyzed.
Occult central neck LN metastasis was present in 54.1% (60/111). Of these patients, bilateral central LN metastases were present in 50% (30/60), unilateral ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of ipsilateral central LN metastasis was significantly higher in male patients, high risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and carcinoma with lymphovascular invasion (P < 0.05). The rate of contralateral central LN metastasis was significantly higher in cases of carcinoma with a maximal diameter of greater than 1 cm, lymphovascular invasion or histologically proven metastasis to the ipsilateral central LN (P < 0.05). Multivariate analysis showed that the tumor size was an independent risk factor for the presence of ipsilateral central LN metastasis, and the presence of ipsilateral central LN metastasis was the only independent predictor for the presence of contralateral central LN metastasis.
Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.
Annals of surgery 05/2009; 249(5):840-4. · 7.90 Impact Factor
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ABSTRACT: Although the KAI1/CD82 protein has been reported to inhibit cell metastasis in many studies, its mechanism of action has not yet been fully elucidated. In the present study, we investigated the possible effects of KAI1/CD82 on the metastatic phenotype in H1299 lung carcinoma cells. These studies were based on the pivotal role that the acquisition of motile phenotype plays on the initial steps of metastasis. KAI1/CD82-mediated morphological changes were observed using phase contrast microscopy. We report here, that a KAI1/CD82-induced phenotypic change was involved in the decrease of Rac1 expression and GTPase activity. However, we found that KAI1/CD82 did not regulate Rac1 mRNA levels. This suggests the existence of another regulatory mechanism of Rac1 protein maturation or activation. To identify the signaling pathway of Rac1 regulation, we investigated the PI3K/Akt/mTOR pathway, since the PI3K/Akt pathway regulates Rac1 activation and mTOR is known to play a regulatory role in protein translation. H1299/CD82-transfectants showed lower mTOR expression and cell growth than the control group. The data obtained from this study suggested that KAI1/CD82 decreased the metastatic phenotype of H1299 lung carcinoma cells by down-regulating Rac1 expression through the PI3K/Akt/mTOR pathway.
Cell Biochemistry and Function 01/2009; 27(1):40-7. · 1.77 Impact Factor
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ABSTRACT: Lung tumor cell DNA copy number alteration (CNA) was expected to display specific patterns such as a large-scale amplification or deletion of chromosomal arms, as previously published data have reported. Peripheral blood mononuclear cell (PBMC) CNA however, was expected to show normal variations in cancer patients as well as healthy individuals, and has thus been used as normal control DNA samples in various published studies. We performed array CGH to measure and compare genetic changes in terms of the CNA of PBMC samples as well as DNA isolated from tumor tissue samples, obtained from 24 non-small cell lung cancer patients. Contradictory to expectations, our studies showed that the PBMC CNA also showed chromosomal variant regions. The list included well-known tumor-associated NTRK1, FGF8, TP53, and TGFbeta1 genes and potentially novel oncogenes such as THPO (3q27.1), JMJD1B, and EGR1 (5q31.2), which was investigated in this study. The results of this study highlighted the connection between PBMC and tumor cell genomic DNA in lung cancer patients. However, the application of these studies to cancer prognosis may pose a challenge due to the large amount of information contained in genetic predisposition and family history that has to be processed for useful downstream clinical applications.
Molecular Biology Reports 12/2008; 36(7):1767-78. · 2.93 Impact Factor
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ABSTRACT: The epidemiologic data on smoking in association with Parkinson disease (PD) is puzzling. A lower incidence of smoking-related malignancies, especially lung cancer, has been reported by several studies in the patients with PD. In this study, we investigated polymorphic variations in the vascular endothelial growth factor (VEGF) gene, which has been proposed having a pivotal role in progressive damage of nigral dopaminergic neurons, between Korean patients with 188 PD and 321 lung cancer patients. There were no significant differences in the tested single-nucleotide polymorphisms (SNPs) between patients with PD and lung cancer; however, one haplotype was significantly different in comparisons between the two diseases. These results suggest that VEGF genetic polymorphisms might help understand the low incidence of lung cancer in the patients with PD.
Archives of gerontology and geriatrics 04/2008; 48(3):287-90. · 1.36 Impact Factor
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ABSTRACT: Recent studies have shown that diesel exhaust particles (DEP) have adverse effects on the respiratory tract in vitro and in vivo, related to various pro-inflammatory cytokines and inflammatory mediators. The inflammation induced by the production of cyclooxygenase (COX)-2, an important mediator of inflammation and tumor promotion, and excess eicosanoids may be central to the pathogenesis of DEP-induced airway inflammation. However, the role of COX-2 in the pathogenesis of DEP-induced lung inflammation remains unclear, especially in vivo. In this study, we demonstrated that treatment with 50 microg/ml of DEP for 24h induced the expression of the COX-2 gene at both the transcriptional and protein levels, which led to an increase in the release of prostaglandin E(2) (PGE(2)) in A549 cells. In addition, the increased levels of COX-2 and PGE(2) by DEP exposure were significantly suppressed by treatment with 50 pg/ml of dexamethasone (Dex). We also showed that exposure to 25 mg/kg of DEP induced the expression of the COX-2 protein in mouse lung tissues, and this increased COX-2 expression was attenuated by pretreatment with 5 mg/kg of Dex. These findings suggest that COX-2 may play an important role in the pathogenesis of DEP-induced pulmonary inflammation, which is effectively inhibited by glucocorticoid treatment.
Toxicology Letters 03/2008; 176(3):178-87. · 3.23 Impact Factor
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ABSTRACT: The KAI1/CD82 protein has been documented as the tumor metastasis suppressor in many types of human cancers. KAI1/CD82 regulates cell motility and invasiveness; however, the mechanism by which this occurs remains to be fully established. Several studies have shown that KAI1/CD82 modulates integrin-dependent signaling. It was suggested that KAI1/CD82 might function to attenuate the beta1 integrin function of inducing cellular migration. A wound-healing and modified Boyden chamber assays were performed to investigate the mechanism of the KAI1/CD82-mediated inhibition of cell migration. It was found that the migratory ability of H1299/CD82 was inhibited. The immunoblotting and biotinylation assays revealed that H1299/CD82 showed significantly decreased expression of the mature form of beta1, which was functional at the cell surface. It was confirmed that KAI1/CD82 regulates the maturation of the beta1 integrin using CD82-specific si-RNA. These results support a model in which KAI1/CD82 attenuates the maturation of the beta1 integrin precursor and thereby suppresses cell migration.
Biochemical and Biophysical Research Communications 09/2007; 359(3):703-8. · 2.48 Impact Factor
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ABSTRACT: Nanoparticles (NPs) have a greater potential to travel through an organism via inhalation than any other larger particles, and could be more toxic due to their larger surface area and specific structural/chemical properties. The aim of this study was to evaluate in vitro biological effects of various inhalable metallic NPs (TiO2, Ag, Al, Zn, Ni). Human alveolar epithelial cells (A549) were exposed to various concentrations of NPs for 24 h. The extent of morphological damage was in the order of m-TiO2 > n-TiO2 > m-silica > n-Ni approximately = n-Zn approximately = n-Ag approximately = n-Al and was affected in a dose-dependent manner. The extent of apoptotic damage measured with two-color flow cytometry was in the order of n-Zn > n- Ni > m-silica > n- TiO2 > m- TiO2 > n-Al > n-Ag. The extent of apoptotic damage measured with DNA fragmentation was in the order of n-Zn approximately = m-silica > n- Ni > m- TiO2 approximately = n- TiO2 approximately = n-Al > n-Ag, indicating no significant difference in the damages by both m-TiO2 and n-TiO2. The extents of apoptotic damages were also affected in a dose-dependent manner. Uptake of no other NPs but n-TiO2 and m-TiO2 into the cells was observed after 24 h exposure. The intracellular generation of ROS was significant with n-Zn but not with the other particles. These results demonstrated that various inhalable metallic NPs (TiO2, Ag, Al, Zn, Ni) could cause cell damages directly or indirectly. More detailed studies on the influence of size, structure, and composition of the NPs are needed to better understand their toxic mechanisms.
Inhalation Toxicology 02/2007; 19 Suppl 1:59-65. · 1.92 Impact Factor
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ABSTRACT: Genomic alterations have been identified in lung cancer tissues and reported in numerous studies. To analyze genomic aberrations in lung cancer patients, we used array comparative genomic hybridization (array CGH) in 14 squamous cell lung carcinoma (SqC) tissues. Copy number gain and loss in chromosomal regions were detected, and the corresponding genes were confirmed by real time PCR. Several frequently altered loci, including gain of 3q (36% of samples), were found. The most frequently identified losses were found at 14q32.33 (21% of samples). The relative degree of chromosomal change was analyzed using log2 ratios. High-level DNA amplifications (>0.8 log2 ratio) were detected at 20 regions in 1p, 2q, 3q, 4q, 6q, 7p, 8q, 9p, 10q, 12q, 14q and 19p. We found that the fold change levels were highest at EVI1 (3q26.2), LPP (3q27-28) and FHF-1 (3q28) gene loci. Our results show that array CGH is a useful tool for identification of gene alteration in lung cancer, and that the above-mentioned genes might represent potential candidate genes for pathogenesis and diagnosis of lung cancer.
Lung Cancer 01/2007; 55(1):43-51. · 3.43 Impact Factor
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ABSTRACT: Diesel exhaust particles (DEP) are known to produce reactive oxygen species (ROS), which induce oxidative stress and inflammation in the lung and respiratory tract. DEP are composed of polycyclic aromatic hydrocarbons (PAH) and their derivatives, redox active semi-quinones, and trace amounts of heavy metals. ROS production was measured by thiobarbituric acid-reactive substances of deoxyribose (TBARS) formation from DEP samples obtained from Korea (DEP-KO), and the Standard Reference Material (SRM) 2975 to explore the role of transition metals. Both DEP-KO and SRM2975 had similar amounts of transition metals, whereas DEP-KO contained more iron, but less copper and zinc, than SRM2975. The water-soluble fraction from SRM2975, but not that from DEP-KO, had a broad absorption in the visible region, but not from DEP-KO, obscuring an accurate absorption measurement of TBARS. Fluorescence measurements of TBARS generation in a water-soluble extract showed that SRM2975 produces more TBARS, but the addition of hydrogen peroxide (H2O2) generated more TBARS in DEP-KO than in SRM2975, consistent with the higher amounts of iron in DEP-KO. The incubation of DEP with iron chelators inhibited the production of TBARS. Finally, a novel use of the fluorogenic spin trap probe, proxyl fluorescamine, enabled the detection of the ROS production from both DEP-KO and SRM2975. Our findings suggested that careful consideration is needed to measure TBARS production in DEP, and that iron in DEP seems to be more important than other transition metals in H2O2-induced ROS generation.
Toxicology in Vitro 10/2006; 20(6):851-7. · 2.78 Impact Factor
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ABSTRACT: To know the effect of adenosine 5'-triphosphate (ATP) on intracellular calcium level and cell proliferation in cervical cancer cells.
Four different human cervical cancer cell lines (Caski, C33A, HeLaS3 and SiHa) were used in this study. The change of intracellular calcium level, cell proliferation and the activity of proliferation- and calcium-related transcription factors by extracellular ATP were examined in these cell lines.
Extracellular ATP induced calcium mobilization, cell proliferation and the activation of NF-kappaB in all cell lines used.
These results suggest that calcium mobilization and NF-kappaB dependent signaling pathway play an important role in the cell proliferation by ATP in cervical cancer.
European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2006; 127(1):110-4. · 1.97 Impact Factor
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ABSTRACT: We conducted a study on the mechanism of KAI1/CD82-mediated suppression of tumor invasiveness and metastasis, and examined its effect on MMP-9 activity and the TIMP1 levels in H1299 human non-small cell lung carcinoma cells. The H1299 human lung carcinoma cells were transfected with pcDNA3.1-CD82 and stable transfectant clones that had a high KAI1/CD82 expression were obtained. We performed Western blot analysis, cell invasion assay, gelatin zymography, and RT-PCR to assess the KAI1/CD82 expression and tumor invasiveness, the MMP-9 activity, the MMP-9 mRNA and protein levels, and the TIMP1 levels in the H1299/CD82 transfectant cells and compared the results with those of the control groups. The H1299/CD82 transfectants exhibited significant suppression of cell invasion, reduced MMP9 enzyme activity, elevated MMP9 mRNA and MMP-9 protein levels, and elevated TIMP1 levels. It may be postulated that KAI1/CD82 over-expression in the H1299 non-small cell lung carcinoma cells suppresses the tumor invasiveness and metastatic potential by inducing MMP9 inactivation via the up-regulation of TIMP1.
Biochemical and Biophysical Research Communications 05/2006; 342(2):655-61. · 2.48 Impact Factor
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ABSTRACT: Human beta-defensin (hBD)-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP) on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8) expression to DEP exposure in interleukin-1 beta (IL-1beta)-stimulated A549 cells.
IL-1beta markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-kappaB activation in IL-1beta-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha. The experiment using two NF-kappaB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-kappaB-mediated pathway.
These results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1beta-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-kappaB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.
Particle and Fibre Toxicology 02/2006; 3:9. · 7.25 Impact Factor
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ABSTRACT: Abstract
Background
Human β-defensin (hBD)-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP) on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8) expression to DEP exposure in interleukin-1 beta (IL-1β)-stimulated A549 cells.
Results
IL-1β markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-κB activation in IL-1β-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-κB and degradation of IκB-α. The experiment using two NF-κB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-κB-mediated pathway.
Conclusion
These results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1β-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-κB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.
Particle and Fibre Toxicology. 01/2006;
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Chung Hun Ryu,
Sae-Woong Kim,
Kyu Hwa Lee,
Joo Yong Lee,
Hongtae Kim,
Woon Kyu Lee,
Byung Hyune Choi, Young Lim,
Young Hoon Kim,
Kweon-Haeng Lee,
Tae-Kon Hwang,
Tae-Youn Jun,
Hyoung Kyun Rha
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ABSTRACT: Neurofibromatosis type 2 (NF2) is the most commonly mutated gene in benign tumors of the human nervous system such as schwannomas and meningiomas. The NF2 gene encodes a protein called schwannomin or merlin, which is involved in regulating cell growth and proliferation through protein-protein interactions with various cellular proteins. In order to better understand the mechanism by which merlin exerts its function, yeast two-hybrid screening was performed and Ral guanine nucleotide dissociation stimulator (RalGDS), a downstream molecule of Ras, was identified as a merlin-binding protein. The direct interaction between merlin and RalGDS was confirmed both in vitro and in the NIH3T3 cells. The domain analyses revealed that the broad C-terminal region of merlin (aa 141-595) is necessary for the interaction with the C-terminal Ras-binding domain (RBD) of RalGDS. Functional studies showed that merlin inhibits the RalGDS-induced RalA activation, the colony formation and the cell migration in mammalian cells. These results suggest that merlin can function as a tumor suppressor by inhibiting the RalGDS-mediated oncogenic signals.
Oncogene 09/2005; 24(34):5355-64. · 6.37 Impact Factor
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ABSTRACT: Diesel exhaust particles (DEPs) are known to induce allergic responses in airway epithelial cells, such as the production of various cytokines via nuclear factor-kappa B (NF-kappaB). However, the intracellular signal transduction pathways underlying this phenomenon have not been fully examined. This study showed that DEP induced NF-kappaB activity via transforming growth factor-beta activated kinase 1 (TAK1) and NF-kappaB-inducing kinase (NIK) in L2 rat lung epithelial cells. DEP induced the NF-kB dependent reporter activity approximately two- to three-fold in L2 cells. However, this effect was abolished by the expression of the dominant negative forms of TAK1 or NIK. Furthermore, it was shown that DEP induced TAK1 phosphorylation in the L2 cells. These results suggest that TAK1 and NIK are important mediators of DEP-induced NF-kappaB activation.
Toxicology Letters 03/2005; 155(2):337-42. · 3.23 Impact Factor
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ABSTRACT: Silica is a causative factor of acute cell injury in pulmonary fibrosis. Inducible cyclooxygenase-2 (COX-2) was suggested to play a role in the process of inflammation and fibrosis. We report that silica induces COX-2 expression in WI-38 fibroblasts. Further analysis showed that silica activated the transcription of COX-2 gene primarily via a nuclear factor (NF)-kB binding site in the promoter. NF-kB-inducing kinase (NIK) and TGF-k activated kinase 1 (TAK1), the upstream signaling molecules of NF-kB, are involved in the silica-mediated COX-2 expression. The Electrophoretic Mobility Shift Assay (EMSA) showed that silica induced the direct binding of NF-kB on the putative binding site in COX-2 promoter. These results suggest that silica activates the human COX-2 gene transcription through the induction of NF-kB activity.
Journal of Environmental Pathology Toxicology and Oncology 02/2005; 24(3):163-74. · 1.00 Impact Factor
