• Title/Summary/Keyword: BCL6

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Comparative Expression of Bcl-2 and NOS2 in Oral White Lesions and Squamous Cell Carcinoma (구강내 백색병소와 편평상피세포암종에서 bcl-2와 NOS2 비교발현에 관한 연구)

  • Shin, Min;Kim, Eun-Cheol
    • Journal of Oral Medicine and Pain
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    • v.24 no.2
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    • pp.145-161
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    • 1999
  • The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

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A Study on the Etching Characateristics of TiW Films using BCl$_3$/SF6/ gas chemistries (BCl$_3$/SF6 gas chemistries에 의한 TiW막의 식각특성 연구)

  • 권광호;김창일;윤선진;김상기;백규하;남기수
    • Journal of the Korean Institute of Telematics and Electronics D
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    • v.34D no.3
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    • pp.1-8
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    • 1997
  • The surface properties after plasma etching of TiW alloy using the chemistries of BCl$_{3}$ and SF$_{6}$ gases with varying mixing ratio have been investigated using XPS(X-ray photoelectron spectrocopy). The elements existed on the etched sampled have been extracted with BCL$_{3}$/SF$_{6}$ ratio and their chemical binding states have also been analysed. It was confirmed that the thickness of native oxide formed on the TiW films is thinner than 10nm by using Ar sputtering. At the same time, the roughness of etched surface has been esamnied using AFM (atomic force microscopy). on the basis of the basis of this results, the relations between the caanges of oxygen contents detected by XPS and the rouhness of etched surface have been discussed. And the etch rate and etched profile of Tiw films have been examined and the changes of the etch rate and etched prfile have been discussed with XPS results. From XPS results, the role of passivation layer consisted of Ti-S compound with XPS results. From XPS results, the role of passivation layer consisted of Ti-S compound has been proposed. Ti-S compound seems to make a role of passivation layer that surpresses Ti-O formation.ion.

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Different Expressions of HIF-$1\alpha$, Bcl-2 and Baxin DU145 Prostate Cancer Cells Transplanted in Nude Mouse between X-Ray and Neutron Irradiation (누드마우스에 주입된 DU-145 전립샘암에서 엑스선과 중성자선에 의한 HIF-$1\alpha$, Bcl-2, Bax 발현의 차이)

  • Kong, Moon-Kyoo;Kang, Jin-Oh;Kim, Sang-Ki;Shin, Dong-Oh;Park, Seo-Hyun;Kim, Chang-Ju;Chang, Hyun-Kyung
    • Radiation Oncology Journal
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    • v.27 no.4
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    • pp.218-227
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    • 2009
  • Purpose: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-$1\alpha$ expression and apoptosis. Materials and Methods: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-$1\alpha$, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. Results: At day 1, HIF-$1\alpha$ and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-$1\alpha$, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-$1\alpha$ expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Conclusion: Neutron irradiation showed a decrease in HIF-$1\alpha$, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-$1\alpha$ expression and subsequent apoptotic protein expressions.

Comparative Study of Anti-Apoptotic Genes, Bcl-2 and P35 for the Suppression of Apoptosis Induced in Suspension Culture of Transformed Trichoplusia ni BTI Tn 5B1-4 Cells

  • Lee, Jong-Min;Sohn, Bong-Hee;Kang, Pil-Don;Lee, Sang-Uk;Chung, In-Sik
    • International Journal of Industrial Entomology and Biomaterials
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    • v.9 no.2
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    • pp.173-181
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    • 2004
  • To delay the onset of apoptosis in the culture, transformed Tn 5B1-4 cells harboring anti-apoptotic genes, bcl-2 and baculovirus p35, have been established and analyzed for their anti-apoptotic ability in suspension culture using spinner flasks. In the suspension culture at agitation speeds of 100 rpm and 200 rpm, the cell growth of cell clone expressing Bcl-2 protein was much higher than other two clones and the maximum cell density of the clone was 6.0 ${\times}$ 10$^{6}$ cells/ml and 6.2 ${\times}$ 10$^{6}$ cells/ml at day three of the incubation. On the other hand, the cell growth of cell clone expressing baculovirus protein P35 was much higher than other two clones in suspension culture at agitation speed of 300 rpm and the maximum cell density of the clone was 6.1 ${\times}$ 10$^{6}$ cells/ml at day three of the incubation. Based on the pattern of genomic DNA laddering and the microscopic observation of apoptotic bodies, the more apoptotic bodies are induced in Tn 5B1-4 control cell clone at higher agitation speed. This result shows that the shear stress can be a main factor in inducing apoptosis in spinner flask culture. At low agitation speed, cell clone expressing Bcl-2 was more effective in delaying the onset of apoptosis than the cell clone expressing P35. On the other hand, at high agitation speed, cell clones expressing baculovirus P35 was more effective in delaying the onset of apoptosis than the cell clone expressing Bcl-2. Therefore, anti-apoptotic genes, bcl-2 and baculovirus p35, can playa distinct role depending on agitation speed in the suspension culture.

Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression

  • Kim, So Yeun;Yoo, Seung-Jun;Ronnett, Gabriele V;Kim, Eun-Kyoung;Moon, Cheil
    • Molecules and Cells
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    • v.38 no.6
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    • pp.535-539
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    • 2015
  • Olfactory stimulation activates multiple signaling cascades in order to mediate activity-driven changes in gene expression that promote neuronal survival. To date, the mechanisms involved in activity-dependent olfactory neuronal survival have yet to be fully elucidated. In the current study, we observed that olfactory sensory stimulation, which caused neuronal activation, promoted activation of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and the expression of Bcl-2, which were responsible for olfactory receptor neuron (ORN) survival. We demonstrated that Bcl-2 expression increased after odorant stimulation both in vivo and in vitro. We also showed that odorant stimulation activated Akt, and that Akt activation was completely blocked by incubation with both a PI3K inhibitor (LY294002) and Akt1 small interfering RNA. Moreover, blocking the PI3K/Akt pathway diminished the odorantinduced Bcl-2 expression, as well as the effects on odorant-induced ORN survival. A temporal difference was noted between the activation of Akt1 and the expression of Bcl-2 following odorant stimulation. Blocking the PI3K/Akt pathway did not affect ORN survival in the time range prior to the increase in Bcl-2 expression, implying that these two events, activation of the PI3K pathway and Bcl-2 induction, were tightly connected to promote post-translational ORN survival. Collectively, our results indicated that olfactory activity activated PI3K/Akt, induced Bcl-2, and promoted long term ORN survival as a result.

Effect of Bcl-2 Inhibitor Treatment on Embryo Developmental Competence, Apoptosis and ER-stress in Pigs (Bcl-2의 저해제 처리에 따른 돼지 수정란의 배발달 능력, 세포 사멸 및 소포체 스트레스 양상)

  • Hong, Joo-Hee;Min, Sung-Hun;Lee, Enok;Son, Hyeong-Hoon;Yeon, Ji-Yeong;Park, Humdai;Koo, Deog-Bon
    • Reproductive and Developmental Biology
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    • v.36 no.3
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    • pp.167-172
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    • 2012
  • The key regulators of apoptosis are the interacting protein of the Bcl-2 family. Bcl-2, an important member of this family, blocks cytochrome C release by sequestering pro-apoptotic BH3-only proteins such as Bid, Bad, Bax and Bim. The pro-survival family members (Bcl-2, Bcl-XL, Bcl-W) are critical for cell survival, since loss of any of them causes cell death in certain cell type. However, its role during early porcine embryonic development is not sufficient. In this study, we traced the effects of Bcl-2 inhibitor, ABT-737, on early porcine embryonic development. We also investigated several indicators of developmental potential, including gene expression (apoptosis-related genes) and apoptosis, which are affected by ABT-737. Porcine embryos were cultured in the PZM-3 medium with or without ABT-737 for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without ABT-737 ($14.7{\pm}3.0$ vs $30.3{\pm}4.8%$, p<0.05). TUNEL assay showed that the number of containing fragmented DNA at the blastocyst stage increased in the ABT-737 treated group compared with control (4.7 vs 3.7, p<0.05). The mRNA expression of the pro-apoptotic gene Bax increased in ABT-737 treated group (p<0.05), whereas expressions of the anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-XL, Bcl-W) decreased (p<0.05). Also, expressions of the ER stress indicator genes (GRP78, XBP-1 and sXBP-1) increased in ABT-737 treated group (p<0.05). In conclusion, Bcl-2 is closely associated with of apoptosis- and ER stress-related genes expressions and developmental potential in pig embryos.

Effects of Ixeris dentata Extract on Radical Oxygen Species and Bcl-2 Family in Human Breast Cancer Cells (씀바귀 추출물이 인체유방암세포의 활성 산소 및 Bcl-2 Family에 미치는 영향)

  • Kim, Hee-Jung;Kang, Keum-Jee
    • Journal of the East Asian Society of Dietary Life
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    • v.24 no.6
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    • pp.739-747
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    • 2014
  • The aim of the study was to determine the effects of Ixeris dentata extract (IDE) on anticancer activity in human breast cancer MDA-MB-231 cells at both cellular and molecular levels. The cells were cultured in the presence of 0, 20, 30 and $40{\mu}g/mL$ Ixeris dentata extract for 24 hours, respectively. At the end of culture, cytochemical analyses for MTT activity, trypan blue dye exclusion, Annexin V-FITC Apoptosis, and radical oxygen species (ROS) were conducted. RT-PCR was also performed to determine whether or not alterations in cell viability affect the Bax/Bcl-2 ratio. MTT assay showed that relative cell viability decreased in a dose-dependent manner (p<0.05). Reduction of cell viability matched well with increased cell membrane permeability as determined by trypan blue dye exclusion test (p<0.05). The rates of intracellular ROS also increased in a similar manner to those of TB-stained cells. There was an associated shift of apoptotic cells from early to late apoptosis between the 30 and $40{\mu}g/mL$. Bax/Bcl-2 ratio significantly increased along with significant decreases in Bcl-2 expression between 30 and $40{\mu}g/mL$ groups (p<0.05). In conclusion, anticancer activity of Ixeris dentata extract is modulated by a reduction in cell viability along with increased membrane permeability, leading to ROS accumulation within cells, and subsequently cell death through an apoptotic pathway that involves Bax and Bcl-2 in human breast cancer MDA-MB-231 cells.

The Etching Properties of Indium Tin Oxide Thin Films in O2/BCl3/Ar Gas Mixture Using Inductively Coupled Plasma (유도결합플라즈마를 이용한 O2/BCl3/Ar가스에 따른 Indium Tin Oxide 박막의 식각 특성 연구)

  • Wi, Jae-Hyung;Woo, Jong-Chang;Kim, Chang-Il
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.23 no.10
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    • pp.752-758
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    • 2010
  • The etching characteristics of indium tin oxide (ITO) thin films in an $O_2/BCl_3/Ar$ plasma were investigated. The etch rate of ITO thin films increased with increasing $O_2$ content from 0 to 2 sccm in $BCl_3$/Ar plasma, whereas that of ITO decreased with increasing $O_2$ content from 2 sccm to 6 sccm in $BCl_3$/Ar plasma. The maximum etch rate of 65.9 nm/m in for the ITO thin films was obtained at 2 sccm $O_2$ addition. The etch conditions were the RF power of 500 W, the bias power of 200 W, the process pressure of 15 mTorr, and the substrate temperature of $40^{\circ}C$. The analysis of x-ray photo electron spectroscopy (XPS) was carried out to investigate the chemical reactions between the surfaces of ITO thin films and etch species.

Regulation of BNIP3 in Normal and Cancer Cells

  • Lee, Hayyoung;Paik, Sang-Gi
    • Molecules and Cells
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    • v.21 no.1
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    • pp.1-6
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    • 2006
  • Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a mitochondrial pro-apoptotic protein that has a single Bcl-2 homology 3 (BH3) domain and a COOH-terminal transmembrane (TM) domain. Although it belongs to the Bcl-2 family and can heterodimerize with Bcl-2, its pro-apoptotic activity is distinct from those of other members of the Bcl-2 family. For example, cell death mediated by BNIP3 is independent of caspases and shows several characteristics of necrosis. Furthermore, the TM domain, but not the BH3 domain, is required for dimerization, mitochondrial targeting and pro-apoptotic activity. BNIP3 plays an important role in hypoxia-induced death of normal and malignant cells. Its expression is markedly increased in the hypoxic regions of some solid tumors and appears to be regulated by hypoxia-inducible factor (HIF), which binds to a site on the BNIP3 promoter. Silencing, followed by methylation, of the BNIP3 gene occurs in a significant proportion of cancer cases, especially in pancreatic cancers. BNIP3 also has a role in the death of cardiac myocytes in ischemia. Further studies of BNIP3 should provide insight into hypoxic cell death and may contribute to improved treatment of cancers and cardiovascular diseases.