• Title/Summary/Keyword: MYC2

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Studies on the Nuclei Adduction and Expression of c-myc Gene by Benzo(a)pyrene and Doxorubicin in Human NC-37 Cells (사람 NC-37 세포에서 Benzo(a)pyrene과 Doxorubicin에 의한 Nuclei내전과 c-myc 유전자의 발현에 대한 연구)

  • 김호찬;정인철;조무연
    • Journal of Life Science
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    • v.8 no.4
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    • pp.400-409
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    • 1998
  • Formation of adduct was studied in benzo(a)pyrene(BP)- and doxorubicin(Dx)-treated human NC-37 cells and isolated nuclei. Major adducts formed were determined by fluorescence absorption spectrophotometery and DNA-lin-ked protein assay. When isolated nuclei were exposed to carcinogens BP and DMBA, and anticancer drugs m-AMSA, ellipticine and Dx, varying degrees of adduct formation occured between DNA-protein complex and these drugs. When the mixture was centrifuged 1.7 M sucrose solution, binding BP and DMBA appeared to be similar between the sediment and the supernatant. When the sediment was centrifuged again with 0.35% polymin-P, the amount of BP bound was 2-fold greater in the protein(1077$\pm$55cpm) than in DNA fraction (470$\pm$20cpm), whereas that of DMBA was 1.6-fold greater in the DNA than in protein fraction. In the case of m-AMSA, ellipticine and Dx, the amount of binding was slightly greater in supernatant than in sediment in centrifugation with 1.7 M sucrose, and more than 3 times greater in the DNA- than in protein- fraction in centrifugation with 0.35% polymin P. DNA fractions which associated with a subset of nonhistone chromosomal protein were isolated from NC-37 cells exposed to $^{3}$H-BP and $^{14}$C-Dx. They were separated into two distince components DNA-S and DNA-P by centrifugation with 2M Nacl chromatin extraction. The results indicated that the amount of $^{3}$H-BP bound was 6.0-fold greater in DNA-P as compared with DNA-S, while that of $^{14}$C-Dx binding appreaed to be 6.2-fold greater in DNA-S than in DNA-P fraction. When $^{3}$H-BP binding wasdetermined in the presence of cold Dx, the amount of binding was reduced only in the DNA-P fraction, indicating that the interaction between DNA and protein is decreased. Gene expression by these drugs, BP treated cells were increased to compare with nomal cells but reduced by treatment with BP-Dx. These results suggest that the protein moiety which tightly bound to DNA-P fraction may play an important role in the regulation of gene expression.

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The Effect of Rice Bran Extract on the Apoptosis Induction of HL-60 Leukemia Cells (미강(Rice Bran) 추출물의 HL-60 백혈병 세포 Apoptosis 유도 효과)

  • Kim, Eun-Ji;Moon, Jungsun;Kang, Jung-Il;Lee, Young-Ki;Koh, Young-Sang;Yoo, Eun-Sook;Kang, Hee-Kyoung;Yim, Dongsool
    • Korean Journal of Pharmacognosy
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    • v.44 no.3
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    • pp.269-274
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    • 2013
  • In this study, we investigated the anticancer effect of rice bran extract in HL-60 human promyelocytic leukemia cells. The extract of rice bran inhibited the proliferation of HL-60 cells. When treated with the rice bran extract, we could observe the apoptotic characteristics such as apoptotic bodies and the increase of sub-G1 hypodiploid cell population, increase of Bax level, decrease of Bcl-2 expression, cleavage of procaspase-3, cleavage of procaspase-9 and cleavage of poly(ADP-ribose) polymerase(PARP) in HL-60 cells. Furthermore, the apoptosis induction of HL-60 cells treated with the rice bran extract was also accompanied by the inactivation of mitogen-activated protein kinases (MAPK) such as ERK1/2 MAPK and p38 MAPK. In addition, the rice bran extract induced the down-regulation of c-myc. These data suggested that the rice bran extract could induce the apoptosis via the inactivation of ERK1/2 MAPK and p38 MAPK, and the down-regulation of c-myc in HL-60 acute pomyelocytic leukemia cells. The results support that the rice bran extract might have potential for the treatment of acute promyelocytic leukemia.

Roles of Transcription Factor Binding Sites in the D-raf Promoter Region

  • Kwon, Eun-Jeong;Kim, Hyeong-In;Kim, In-Ju
    • Animal cells and systems
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    • v.2 no.1
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    • pp.117-122
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    • 1998
  • D-raf, a Drosophila homolog of the human c-raf-1, is known as a signal transducer in cell proliferation and differentiation. A previous study found that the D-raf gene expression is regulated by the DNA replication-related element (DRE)/DRE-binding factor (DREF) system. In this study, we found the sequences homologous to transcription factor C/EBP, MyoD, STAT and Myc recognition sites in the D-raf promoter. We have generated various base substitutional mutations in these recognition sites and subsequently examined their effects on D-raf promoter activity through transient CAT assays in Kc cells with reporter plasmids p5'-878DrafCAT carrying the mutations in these binding sites. Through gel mobility shift assay using nuclear extracts of Kc cells, we detected factors binding to these recognition sites. Our results show that transcription factor C/EBP, STAT and Myc binding sites in D-raf promoter region play a positive role in transcriptional regulation of the D-raf gene and the Myo D binding site plays a negative role.

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Identification of Soil Actinomycetes Producing Anticancer Agent and Its Biological Activities (항암활성물질을 생산하는 토양방선균의 동정 및 함암물질의 생물학적 활성)

  • 박정민;문순옥;오두환
    • Microbiology and Biotechnology Letters
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    • v.22 no.4
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    • pp.347-352
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    • 1994
  • Cytotoxic test was performed by SRB assay on human epidermoid carcinoma HEp-2 cell line for screening the soil microorganism, secreting anticancer agent. One microorganism was selected among two thousand microorganisms for its highest cytotoxicity. And this microorganism was identified with Streptomyces species after performing of diaminopimeric acid and reducing sugar analysis of cell wall and analysing the cultural characteristics and named Streptomyces sp. SM 1119. The effect of anticancer agent in SM 1119 culture extract on the cell cycle was studied by using GG$_{o}$ synchronized NIH 3T3 cells. The extract inhibited the serum stimulation of GG$_{o}$ NIH 3T3 cell only within 1 hour after serum stimulation but not after 6 hours. The extract also reduced the amount of c-myc mRNA in Colo 320 cell. These results suggest that the anticancer agent in the extract inhibits the progression of cell cycle very early stages, probably from G$_{0}$ to G$_{1}$.

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Stemness and Proliferation of Murine Skin-Derived Precursor Cells under Hypoxic Environment

  • Kim, Hyewon;Park, Sangkyu;Roh, Sangho
    • International Journal of Oral Biology
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    • v.41 no.2
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    • pp.69-74
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    • 2016
  • Skin-derived precursors (SKPs) have potential to differentiate to various cell types including osteoblasts, adipocytes and neurons. SKPs are a candidate for cell-based therapy since they are easily accessible and have multipotency. Most mammalian cells are exposed to a low oxygen environment with 1 to 5% $O_2$ concentration in vivo, while 21% $O_2$ concentration is common in in vitro culture. The difference between in vitro and in vivo $O_2$ concentration may affect to the behavior of cultured cells. In this report, we investigated the effect of hypoxic condition on stemness and proliferation of SKPs. The results indicated that SKPs exposed to hypoxic condition for 5 days showed no change in proliferation. In terms of mRNA expression, hypoxia maintained expression of stemness markers; whereas, oncogenes, such as Klf4 and c-Myc, were downregulated, and the expression of Nestin, related to cancer migration, was also downregulated. Thus, SKPs cultured in hypoxia may reduce the risk of cancer in SKP cell-based therapy.

Effects of Lonicerae Caulis (LC) on Gene Expression of Human melanoma cells (인동등(忍冬藤)이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향)

  • Kim, Dae-Su;Choi, Jeong-Hwa;Kim, Jong-Han;Park, Soo-Yeon;kang, Seong-In
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.1
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    • pp.11-32
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    • 2009
  • Objective : This study was designed to investigate anti-cancer and whitening activities (LC). So it was investigated the effects of LC on proliferation rates of melanoma genetic profile by LC. Methods : The genetic profile for the effect of LC on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes were conducted. Total 441 genes were up-regulated and 830 genes down-regulated in cells treated with LC. Genes induced or suppressed by LC were all mainly concerned with basic signalling pathways, which are involved in cell growth, differentiation and migration. Especially, many genes, which are related in apoptosis and cell cycle arrest were up-regulated by treatment with LC, and genes related in cell cycle were down-regulated. Result : The network of total protein interactions were identified by using cytoscape program, and some key molecules, such as BCL2L1, SIN3A, SMAD2 and c-myc that can be used for elucidation of therapeutical mechanism of medicine in the future. Conclusion : These results suggest possibility of LC as addition drug and whitening cosmetics. In addition, it was also suggested that related mechanisms are involved in BCL2L1, SIN3A, SMAD2 and c-myc related signalling pathways.

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RNases and their role in Cancer

  • Beeram, Eswari
    • The Korean Journal of Food & Health Convergence
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    • v.5 no.2
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    • pp.27-34
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    • 2019
  • RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

$In$ $vitro$ MRI and Characterization of Rat Mesenchymal Stem Cells Transduced with Ferritin as MR Reporter Gene (페리틴 리포터 유전자를 발현하는 백서 중간엽 줄기세포의 특성과 자기공명영상 연구)

  • Shin, Cheong-Il;Lee, Whal;Woo, Ji-Su;Park, Eun-Ah;Kim, Pan-Ki;Song, Hyun-Bok;Kim, Hoe-Suk
    • Investigative Magnetic Resonance Imaging
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    • v.16 no.1
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    • pp.47-54
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    • 2012
  • Purpose : This study was performed to evaluate the characteristics of rat mesenchymal stem cells (RMSCs) transduced with human ferritin gene and investigate $in$ $vitro$ MRI detectability of ferritin-transduced RMSCs. Materials and Methods: The RMSCs expressing both myc-tagged human ferritin heavy chain subunit (myc-FTH) and green fluorescence protein (GFP) were transduced with lentiviurs. Transduced cells were sorted by GFP expression using a fluorescence-activated cell sorter. Myc-FTH and GFP expression in transduced cells were detected by immunofluorescence staining. The cell proliferative ability and viability were assessed by MTT assay. The RMSC surface markers (CD29+/CD45-) were analyzed by flow cytometry. The intracellular iron amount was measured spectrophotometically and the presence of ferritin-iron accumulation was detected by Prussian blue staining. $In$ $vitro$ magnetic resonance imaging (MRI) study of cell phantoms was done on 9.4 T MR scanner to evaluate the feasibility of imaging the ferritin-transduced RMSCs. Results: The myc-FTH and GFP genes were stably transduced into RMSCs. No significant differences were observed in terms of biologic properties in transduced RMSCs compared with non-transduced RMSCs. Ferritin-transduced RMSCs exhibited increased iron accumulation ability and showed significantly lower $T_2$ relaxation time than non-transduced RMSCs. Conclusion: Ferritin gene as MR reporter gene could be used for non-invasive tracking and visualization of therapeutic mesenchymal stem cells by MRI.

High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells

  • Hu, Jinfang;Zhang, Zhiguo;Zhao, Lei;Li, Li;Zuo, Wei;Han, Lei
    • BMB Reports
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    • v.52 no.2
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    • pp.151-156
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    • 2019
  • RAD51 recombinase plays a critical role in homologous recombination and DNA damage repair. Here we showed that expression of RAD51 is frequently upregulated in lung cancer tumors compared with normal tissues and is associated with poor survival (hazard ratio (HR) = 2, P = 0.0009). Systematic investigation of lung cancer cell lines revealed higher expression of RAD51 in KRAS mutant (MT) cells compared to wildtype (WT) cells. We further showed that MT KRAS, but not WT KRAS, played a critical role in RAD51 overexpression via MYC. Moreover, our results revealed that KRAS MT cells are highly dependent on RAD51 for survival and depletion of RAD51 resulted in enhanced DNA double strand breaks, defective colony formation and cell death. Together, our results suggest that mutant KRAS promotes RAD51 expression to enhance DNA damage repair and lung cancer cell survival, suggesting that RAD51 may be an effective therapeutic target to overcome chemo/radioresistance in KRAS mutant cancers.

Microsatellite Instability and p53, k-ras c-myc Oncoprotein Expression in Non-Small Cell Lung Carcinoma (비소세포 폐암에서의 Microsatellite Instability와 p53. K-ras, c-myc 암단백의 발현)

  • 나석주;곽문섭
    • Journal of Chest Surgery
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    • v.33 no.1
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    • pp.60-67
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    • 2000
  • Background: Microsatellites are short-tandem repeated uncleotide sequences present throughout the human genome. Alterations of microsatellites have been termed microsatellite instability(MI). It has been generally known that microsatellite instability detected in hereditary non-polyposis colorectal cancer (HNPCC) reflects genetic instability that is caused by impairments of DNA mismatch repair system regarding as a novel tumorigenic mechanism. A number of studies reported that MI occurred at varying frequencies in non-small cell lung carcinoma (NSCLC). However It has been unproven whether MI could be a useful market of genetic instability and have a clinical significance in NSCLC. Material and Method : We have examined whether MI can be observed in thirty NCSLC using polymerase chain reaction whether such alterations are associated with other molecular changes such as p53, K-ras and c-myc oncoproteins expression detected by immunohistochemical stain,. Result: MI(+) was observed in 16.6%(5/30) and MI(-) was 83.3% (25/30) Average age was 50$\pm$7.5 year-old in MI(+) group and 57$\pm$6.6 year-old in MI(-) group. Two year survival rate in MI(=) group (20% 1/5) was worse than MI(-) group (64% 16/25) with a statistic difference. (P=0.04) The positive rate of K-ras oncoprotein expression and simultaneous expression of 2 or 3 oncoproteins expression were higher in MI(+) group than MI(-) group with a statistic difference(P=0.05, P=0.01) Conclusion: From, these results the authors can conclude that MI is found in some NSCLC and it may be a novel tumorigenic mechanism in some NSCLC. We also conclude that MI could be used as another poor prognostic factor in NSCLS.

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