• The Korean Journal of Zoology
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• v.39 no.4
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• pp.352-361
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• 1996

The c-myc proto-onco9ene, one of the immediately early genes, is involved in ceflular proliferation and differentiation, and its biologleal function is regulated hy dimerization with a heterodimeric partner, myn. In the present study, gene expression patterns of c-myc and myn during mouse preimplantation embryo development were examined using a semi-quantitative reverse transcription-poiymerase chain reaction (RT-PCR). Myn transcripts were rather constitutively expressed throughout embryonic stages with a slight increase only at biastocyst stage. in contrast, expression of c-myc transcripts wm developmental stage-'pedfic. The c-myc transcripts were detected at 1-cell stage, declined abruptly at 2-cell stage and then increased gradually at blastocyst stage. To examine the possible role of myn during preimpiantation mouse embryo development, two myn antisense oligonucleotides spanning the tail of zipper dognain (myn2; 20-mer) and the second helix domain (myn3; 20-mer) were microinjected into the fertilized 1-cellembryos. Microinjection of myn2 and myn3 resulted in developmental tion at morula/biastocyst transition stage, leading to the fiagentation of embryos. Talien together, these results suggest that c-myc and its heterodimeric partner, myn, are differentially expressed In a developmental stage-dependent manner, and myn may play an important role in mouse preimpiantation embryo development.

• Journal of Plant Biotechnology
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• v.44 no.4
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• pp.409-415
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• 2017

The vegetation period of trees might be prolonged by the delay of the leaf senescence in autumn. Thus, we focused on the generation of senescence-delayed transgenic trees to enhance biomass production. The PagMYC2, a gene containing the basic helix-loop-helix domain, was selected as a candidate for a senescence-delayed transgenic tree. The PagMYC2 gene was specifically induced after treatment with phytohormone jasmonic acid, and upregulated by abiotic stresses such as salinity, osmotic pressure and a low temperature. The constitutive overexpression of the PagMYC2 delayed the leaf senescence and inhibited chlorophyll degradation in the transgenic poplars. Leaf senescence analysis was performed in the leaf tissues of the PagMYC2-over-expression transgenic poplars. The transgenic poplars exhibited higher photochemical efficiency than did a wild type plant under a short-day condition (6 hours light/18 hours darkness) or a low temperature condition ($15^{\circ}C$) that was similar to the weather conditions of autumn. These results suggest that the PagMYC2 is a useful genetic resource to improve biomass production, which is able to sustain growth with senescence-delayed leaves for a long time in autumn.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5807-5815
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• 2015

Background: Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. Materials and Methods: This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Conclusions: The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.

• 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.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.215-233
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• 2023

Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.6
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• pp.1024-1030
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• 1996

Capsaicin (8-methyl-N-vanillyl-6-nonenamide: CAP) is a mai or ingredient of hot pepper that has been used as a spicy food additive, preservative, and medicine. In this study, we evaluated the effect of dietary CAP on the selected proto-oncogene(c-jun, c-myc, H-ras, erbB, p53) expressions in various tissues of mice. Male ICR mice were divided into four groups and fed the experimental diets containing CAP at the levels of 0, 5, 20 and 100ppm for four weeks. Steady state RNA levels in various tissues were measured by slot blot hybridization assay. C-jun expression level was enhanced in stomach tissue from mice fed 20ppm CAP and significantly reduced from mice fed 100ppm CAP. The c-jun expression levels were differentially altered in organ-specific manner, Tumor suppressor gene p53 expression level appeared to be slightly increased in the liver from mice fed 20ppm CAP. These results suggested that dietary CAP differentially modulates c-jun and p53 expression in various organs.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7061-7069
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• 2015

Background: During the past decades, the incidence and mortality rate of stomach cancer has demonstrated a great decrease in the world, but it is still one of the most common and fatal cancers especially among men worldwide, including Iran. The MYC proto-oncogene, which is located at 8q24.1, regulates 15% of genes and is activated in 20% of all human tumors. MYC amplification and overexpression of its protein product has been reported in 15-30% of gastric neoplasias. The aim of this investigation was to find the relative efficacy of CISH (chromogenic in situ hybridization) or IHC (immunohistochemistry) in diagnosis and prognosis of gastric cancer, as well as the relationship of amplification and expression of C-MYC gene with patient survival. Materials and Methods: In this cross-sectional study, 102 samples of gastric cancer were collected from patients who had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences, from July 2009 to March 2014. All samples were randomly selected from those who were diagnosed with gastric adenocarcinomas. CISH and IHC methods were performed on all of them. Results: Patients were classified into two groups. The first consisted of stage I and II cases, and the second of stage III and IV. Survival tests for both groups was carried out with referrnce to CISH test reults. Group II (stage III & IV) with CISH+ featured lower survival than those with CISH- (p=0.233), but group I (stage I & II) patients demonstrated no significant variation with CISH+ or CISH- (p=0.630). Kaplan-Meier for both groups was carried out with IHC test findings and showed similar results. This data revealed that both diffuse and intestinal types of gastric cancer occurred significantly more in men than women. Our data also showed that CISH+ patients (43%) were more frequent in comparison with IHC+ patients (14.7%). Conclusions: For planning treatment of gastric cancer patients, by focusing on expanding tumors, which is the greatest concern of the surgeons and patients, CISH is a better and more feasible test than IHC, in regard to sensitivity and specificity. Therefore, CISH can be used as a feasible test for tumor growth and prognosis in stage III and IV lesions. This study also indicated that C-MYC amplification in gastric cancer is correlated with survival in advanced stages.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.19-27
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• 1999

Apoptosis has been implicated in the pathophysiological mechanisms of various neurodegenerative diseases. In a variety of cell types, oxidative stress has been demonstrated to play an important role in the apoptotic cell death. However, the exact mechanism of oxidative stress-induced apoptosis in neuronal cells is not known. In this study, we induced oxidative stress in IMR-32 human neuroblastoma cells with tert- butylhydroperoxide (TBHP), which was confirmed by significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity. TBHP induced decrease in cell viability and increase in DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TBHP also induced a sustained increase in intracellular $Ca^{2+}$ concentration, which was completely prevented either by EGTA, an extracellular $Ca^{2+}$ chelator or by flufenamic acid (FA), a non-selective cation channel (NSCC) blocker. These results indicate that the TBHP-induced intracellular $Ca^{2+}$ increase may be due to $Ca^{2+}$ influx through the activation of NSCCs. In addition, treatment with either an intracellular $Ca^{2+}$ chelator (BAPTA/AM) or FA significantly suppressed the TBHP-induced apoptosis. Moreover, TBHP increased the expression of p53 gene but decreased c-myc gene expression. Taken together, these results suggest that the oxidative stress-induced apoptosis in neuronal cells may be mediated through the activation of intracellular $Ca^{2+}$ signals and altered expression of p53 and c-myc.

• Biomedical Science Letters
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• v.3 no.1
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• pp.11-20
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• 1997

A regulation of differentiation in human neuroblastoma cells remains poorly understood, although it is of great importance in the clinical therapy of neuroblastoma. This study was aimed to elucidate effects of DNA synthesis inhibitors on the differentiation of neuroblastoma cells on the basis of morphological, biochemical and molecular respects. Three DNA synthesis inhibitors, sodium butyrate, hydroxyurea, cytosine arabinoside were used to explore their effects on the cellular morphology, the expression of c-myc and the elevation of choline acetyltransferase activity. They led to the extension or neurite-like processes reflecting differentiation or IMR-32 cells. In addition, the treatment of three DNA synthesis inhibitors resulted in the remarkable increases in the expression of c-myc as well as the stimulation of choline acetyltransferase activity which is involved in the synthesis of acetylcholine in the differentiated cholinergic neurons. Taken together, these results indicate that DNA synthesis inhibitors play an important role in the induction of cellular differentiation in IMR-32 cells. Furthermore these DNA synthesis inhibitors seem to be future useful to give an important clue (for the treatment of neuroblastoma).