• Title/Summary/Keyword: late gene

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Involvement of Early Growth Response Gene 1 (EGR-1) in Growth Suppression of the Human Colonic Tumor Cells By Apigenin and Its Derivative Isovitexin (Apigenin과 대사물 isovitexin에 의한 인체 대장암세포의 세포활성 억제효과에 있어서의 EGR-1의 역할 연구)

  • Moon, Yu-Seok;Cui, Lei-Guang;Yang, Hyun
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.110-115
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    • 2007
  • It has been previously described that transcription factor early growth response gene product 1 (EGR-1) functions as a tumor suppressor gene. This study was conducted to demonstrate that EGR-1 induction by phytochemical apigenin and its derivative isovitexin can mediate the growth suppression of the intestinal epithelial tumor cells. Apigenin and isovitexin induced EGR-1 gene expression both in the dose and time-dependent manners. Moreover the induction was relatively late around 9-12 hr after treatment of HCT-116 cells, while several anti-inflammatory agent such as NSAIDS and catechins elicit the ECR-1 gene expression at much earlier time about 1-3 hr after treatment. In terms of signal transduction, ERK1/2 was critical for apigenin-induced EGR-1 gene expression and its promoter activation. When EGR-1 gene expression was blocked with EGR-1 small interference RNA, the cytotoxicity of apigenin in the human epithelial cells was attenuated, suggesting the involvement of EGR-1 in the anti-tumoric activity of apigenin. To link the EGR-1 induction to EGR-1-regulated gene products in colon cancer, NSAID-Activated Gene 1 (NAG-1) was demonstrated to be elevated by apigenin and isovitexin at 24-48 hr after treatment. Taken together, apigenin-activated ERK1/2 mediated EGR-1 gene induction, which was associated with suppression of the cellular viability by apigenin compound.

Tumorigenicity of benzo(a)pyrene and benzo(a)pyrene diol epoxides in v-Ha-ras transgenic TG-AC mice

  • Lee Byung Mu;Germolec Dori;Jeohn Kwang-Ho;Tennant Raymond W,
    • Proceedings of the Korean Society of Toxicology Conference
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    • 1998.10a
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    • pp.36-36
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    • 1998
  • Tumorigenicity of benzo(a)pyrene (BP) and benzo(a)pyrene diol epoxides ((+)BPDE-1, (-)BPDE-1) was investigated in transgenic TG-AC mice carrying v-Ha-ras oncogene fused to the promoter of the mouse embryonic a-like, z-globin gene. Animals were topically treated twice per week for 25weeks with BPDE (10$\mu$g/mouse) and BP (10, 20, 40$\mu$g/mouse). In addition, animals were treated with BPDE or BP (initiated) followed by TPA (2$\times$2.5$\mu$g/week, for 4 weeks) for promotion study. In the continuous treatment of BPDE or BP, animals treated with 40$\mu$g BP showed $100\%$ tumor response after 20 weeks, $40\%$ of mice for 20$\mu$g BP, and $20\%$ for (+)BPDE-1, but (-)BPDE-1 and 10$\mu$g BP did not show any tumor response. After 25 weeks, most tumors turned out to be carcinomas in animals treated with 40$\mu$g BP. In BPDE or BP/TPA Initiation-promotion study, papilloma response occurred earlier (6 weeks after TPA treatment) than in continuously treated animals with BPDE or BP. RT-PCR assay for transgene expression showed that BP or BPOE was not transgene dependent in its tumorigenicity, but TPA was. Several Cytokine genes(TGF-a, TNF-a) and c-myc gene expressions were monitored in skin tissues during BP carcinogenesis. In early stage of BP treatment, the gene expressions were elevated(c-myc,TGF-a) or unchanged(TNF-a) compared to control, but the levels were gradually decreased during both middle and late stages of cacinogenesis, Gene expression levels of skin papillomas in acetone initiated-TPA promoted animals were close to those of middle stage or between middle and late stages. i-NOS was also highly expressed in carcinoma and papilloma, These data suggest that transgene expressions of TG-AC mice were not dependent on BP carcinogenesis and that TG-AC mice were more sensitive to TPA regardless of types of initiators. In addition, genes(TGF-a, c-myc, TNF-a, i-NOS) were modulated in the skin during BP cacinogenesis or TPA promotion.

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Predictive Value of Xrcc1 Gene Polymorphisms for Side Effects in Patients undergoing Whole Breast Radiotherapy: a Meta-analysis

  • Xie, Xiao-Xue;Ouyang, Shu-Yu;Jin, He-Kun;Wang, Hui;Zhou, Ju-Mei;Hu, Bing-Qiang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6121-6128
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    • 2012
  • Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

Regulation of Corynebacterium ammoniagenes purF and Isolation of purF-Specific Regulatory Proteins (Corynebacterium ammoniagenes에서 purF 유전자의 조절 및 이에 특이적인 조절 단백질의 분리)

  • Lee, Seok-Myung;Kim, Youn-Hee;Lee, Heung-Shick
    • Korean Journal of Microbiology
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    • v.45 no.3
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    • pp.233-238
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    • 2009
  • The expression of Corynebacterium ammoniagenes purF was analyzed by utilizing a plasmid carrying a cat gene fused to the purF promoter region. Adenine and guanine repressed the expression of the purF gene by 20~30% but hypoxanthine did not exert such repressive effect. The expression purF was maximal at the late log phase and remained constant throughout the stationary phase. Promoter $P_{180}$ which was developed in C. glutamicum was also functional in C. ammoniagenes, achieving maximal activity at the late log phase. The promoter outperformed Escherichia coli $P_{tac}$ promoter by 40~50% level. DNA-affinity purification identified a protein which could bind to the promoter region of the purF gene. The protein showed high similarity to the CRP-family transcriptional regulator encoded by NCgl0120 in C. glutamicum. The size of the screened protein agreed with the expected protein size from the ORF NCgl0120. The corresponding gene in C. ammoniagenes encoded a 42 kDa polypeptide composed of 400 amino acids with expected pI of 4.9. The encoded protein showed 14.1% and 15.8% identity with E. coli and Bacillus subtilis PurR, respectively, suggesting that the isolated protein might be a novel type of regulatory protein involved in the regulation of purine metabolism.

Late-onset drug resistant epilepsy in an adolescent with Allan-Herndon-Dudley syndrome

  • Soyoung Park;Young-Lim Shin;Go Hun Seo;Yong Hee Hong
    • Journal of Genetic Medicine
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    • v.21 no.1
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    • pp.31-35
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    • 2024
  • Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder with abnormal thyroid function caused by mutation in the solute carrier family 16 member 2 (SLC16A2) gene. Clinical manifestations of AHDS are global or axial hypotonia, a variety of movement disorders, severe intellectual disability, quadriplegia or spastic diplegia, growth failure, and seizures. A 10-year-old boy visited our hospital with the chief complaint of newly onset generalized tonic seizures with vocalization of weekly to daily frequency. He showed early infantile hypotonia, severe intellectual disability, and frequent respiratory infections. He could not walk independently and was non-verbal. Electroencephalogram revealed generalized slow spike and waves with multifocal spikes and slow background rhythms. His tonic seizures were controlled with more than two anti-seizure medications (ASMs). At 11 years of age, he was evaluated for thyroid function as part of regular screening for ASM maintenance and was found to have abnormal thyroid function. We performed whole exome sequencing for severe global developmental delay, drug-resistant epilepsy, and abnormal thyroid function. The hemizygous c.940C>T (p.Arg314Ter) variant in the SLC16A2 gene (NM_006517.5) was identified and confirmed based on Sanger sequencing. Herein, we describe a case of an AHDS patient with late-onset drug-resistant epilepsy combined with congenital hypotonia, global developmental delay, and abnormal thyroid function results. To the best of our knowledge, this is the oldest adolescent among AHDS cases reported in Korea. In this report, clinical characteristics of a mid-adolescence patient with AHDS were presented.

Characterization of disease outbreak pattern of transgenic potato plants with the coat protein gene of Potato leaf roll virus.

  • Shin, D.B.;Cheon, J.U.;Jee, J.H;Lee, S.H.;Park, H.S.;Park, J.W
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.121.2-122
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    • 2003
  • Since the demonstration that the transgenic plants expressing tobacco mosaic virus(TMV) coat protein(CP) gene showed resistance to TMV infection, there have been numerous attempts to produce virus-resistant plant by introducing of a part of or modified viral genome. This study was conducted to investigate the characterization and variability of disease outbreak of transgenic potato(T-potato) with the CP gene of potato leaf roll virus(PLRV) in an isolated field from 2000 to 2002. In the field inspection, incidence of PLRV on T-potato showed only 3.5%, while non-transgenic potato(N-potato) revealed 13.4%. Infection rate of PLRV was considerably low on T-potato with 4.2% compared to 15.4% of N-potato in ELISA tests. Those of potato virus M, potato virus Y and potato virus X on both potatoes were not statistically different. Infection of potato virus A was not observed on both potatoes. Incidence of potato late blight caused by Phytopkhora infestans on T-potato and N-potato did not differ each other with 52.7%, and 50.8%, respectively, Mating type of the causal fungus isolated from both potatoes was all Al types. Results indicates that the CP gene of PLRV affects specifically to the virus in the transgenic potato.

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An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model

  • Kwon, Jung Hyun;Kim, Kwan Chang;Cho, Min-Sun;Kim, Hae Soon;Sohn, Sejung;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.56 no.3
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    • pp.116-124
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    • 2013
  • Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

The Phylogenetic Relationship of Several Oscillatorian Cyanobacteria, Forming Blooms at Daecheong Reservoirs, Based on Partial 16S rRNA Gene Sequences

  • Lee, Wook-Jae;Bae, Kyung-Sook
    • Journal of Microbiology and Biotechnology
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    • v.11 no.3
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    • pp.504-507
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    • 2001
  • The partial 16S gene sequences of six filamentous cyanobacterial strains, Oscillatoria lmosa KCTC AG10168, Oscillatoria princeps KCTC AG10153, Oscillatoria sp. KCTC AG 10184, Phormidium tenue KCTC AG10158, Phormidium parchydematicum KCTC AG10164, and Lyngbya hieronymusii KCTC AG10199, which were isolated in the late summer at Daecheong Reservoirs, were determined and assigned their phylogenetic and taxonomic position among taxa of order Ocillatoriales whose partial 16S rRNA gene sequences aligned in this suty, were very heterogeneously clustered with other taxa. The two strains, Oscillatoria limosa KCTC AG10168 and O. princeps KCTC AG10153, formed a cluster with O. sancta PCC7515, which supported 64% of the bootstrap trees with high similarity (19-96.15%). Strain Oscillatoria sp. KCTC AG10184, that was known to produce a nasty substance, was closely related to the toxic Oscillatoria group. The study on morphological variation in various environments and toxin production will confirm the taxonomic status of these species. Phormidium tenus KCTC AG10158 and Phormidium parchydematicum KCTC AG10164 made a cluster with other oscillatorian species of Phormidium, Oscillatoria, and Leptolynbya, which supproted 100% of the bootstrap trees with a very high sequence smilarity (96.8-99.8%) in thsi study. The sequence analysis in this study also supported that taxa of oscillatoriales are not monophyletic. Some of the fractures, such as the presence or absence of sheath and cell shape, which were used to define them, would be inadequate and should be reconfirmed. We suggest that sequences of partial 16S rRNA gene fragments aligned in this study should be more useful than morphological features in the identification and reconfirmation of the taxonomic status of these oscillactorian cyanobacteria.

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Identification and Characterization of a Conserved Baculoviral Structural Protein ODVP-6E/ODV-E56 from Choristoneura fumiferana Granulovirus

  • Rashidan, Kianoush Khajeh;Nassoury, Nasha;Giannopoulos, Paresa N.;Guertin, Claude
    • BMB Reports
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    • v.35 no.6
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    • pp.595-603
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    • 2002
  • A gene that encodes a homologue to baculoviral ODVP-6E/ODV-E56, a baculoviral envelope-associated viral structural protein, has been identified and sequenced on the genome of Choristoneura fumiferana granulovirus (ChfuGV). The ChfuGV odvp-6e/odv-e56 gene was located on an 11-kb BamHI subgenomic fragment using different sets of degenerated primers, which were designed using the results of the protein sequencing of a major 39 kDa structural protein that is associated with the occlusion-derived virus (ODV). The gene has a 1062 nucleotide (nt) open-reading frame (ORF) that encodes a protein with 353 amino acids with a predicated molecular mass of 38.5 kDa. The amino acid sequence data that was derived from the nucleotide sequence in ChfuGV was compared to those of other baculoviruses. ChfuGV ODVP-6E/ODV-E56, along with othe baculoviral ODVP-6E/ODV-E56 proteins, all contained two putative transmembrane domains at their C-terminus. Several putative N-and O-glycosylation, N-myristoylation, and phosphorylation sites were detected in the ChfuGV ODVP-6E/ODV-E56 protein. A similar pattern was detected when a hydrophobicity-plots comparison was performed on ChfuGV ODVP-6E/ODV-E56 with other baculoviral homologue proteins. At the nucleotide level, a late promoter motif (GTAAG) was located at -14 nt upstream to the start codon of the GhfuGV odvp-6e/odv-e56 gene. a slight variant of the polyadenylation signal, AATAAT, was detected at the position +10 nt that is downstream from the termination signal. A phylogenetic tree for baculoviral ODVP-6E/ODV-E56 was constructed using a maximum parsimony analysis. The phylogenetic estimation demonstrated that ChfuGV ODVP-6E/ODV-E56 is most closely related to those of Cydia pomonella granulovirus (CpGV) and Plutella xylostella granulovirus (PxGV).

p13 from group II baculoviruses is a killing-associated gene

  • Lu, Nan;Du, Enqi;Liu, Yangkun;Qiao, Hong;Yao, Lunguang;Pan, Zishu;Lu, Songya;Qi, Yipeng
    • BMB Reports
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    • v.45 no.12
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    • pp.730-735
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    • 2012
  • p13 gene was first described in Leucania separata multinuclear polyhedrosis virus (Ls-p13) several years ago, but the function of P13 protein has not been experimentally investigated to date. In this article, we indicated that the expression of p13 from Heliothis armigera single nucleocapsid nucleopolyhedrovirus (Ha-p13) was regulated by both early and late promoter. Luciferase assay demonstrated that the activity of Ha-p13 promoter with hr4 enhancer was more than 100 times in heterologous Sf9 cells than that in nature host Hz-AM1 cells. Both Ls-P13 and Ha-P13 are transmembrane proteins. Confocal microscopic analysis showed that both mainly located in the cytoplasm membrane at 48 h. Results of RNA interference indicated that Ha-p13 was a killing-associated gene for host insects H. armigera. The AcMNPV acquired the mentioned killing activity and markedly accelerate the killing rate when expressing Ls-p13. In conclusion, p13 is a killing associated gene in both homologous and heterologous nucleopolyhedrovirus.