• The Korean Journal of Zoology
• /
• v.38 no.4
• /
• pp.550-556
• /
• 1995

The c-myc proto-oncogene is Involved In the control of normal cell proliferation and differentiation of many cell lineages. Although it has heen suggested that c-myc may play an important role in the mammalian early development, it Is unclear whether the embryonic c-myc mRNA is originated from zygotic gene expression or stored maternal message. Thus, we have construded expression vectors, In which the 5, flanking sequences including c-myc promoter region and a large non-coding exon I are fused 'sith E. coli lacZ gene that encedes $\beta$-galactosldase as a reporter. As c-myc exon I contains a modulatory sequence, we designed t, vo types of vectors (pcmyc.Gall and pcmyc-Ga12) to examine the role of exon I in c-myc expression. The former contains the complete exon I and the later has a deletion in 40 bp of modulator sequence located In the exon I of c-myc These vectors were microInjected into fertilized one-cell embryos and $\beta$-galactosidase activity was examined by X-gal staining during early embryogenesis. $\beta$-galactosidase activity derived from c-myc promoter was decreased at two-cell stage. The expression level directed by pcmyc- Ga12 was similar to that of pcmyc-Gal1, indicating that the medulatory sequence in exon I may not be Involved at least In the regulation of embryonic c-myc expression. In summary, the present study indicates that the c-myc promoter is functional at the early stage embryo, and the regulation of c-myc expression is under the control of "zygotic" clock of preimplantation mouse embryos.e embryos.

• Molecules and Cells
• /
• v.20 no.2
• /
• pp.157-166
• /
• 2005

The c-myc proto-oncogene encodes a nuclear protein that is deregulated and/or mutated in most human cancers. Acting primarily as an activator and sometimes as a repressor, MYC protein controls the synthesis of up to 10-15% of genes. The key MYC targets contributing to oncogenesis are incompletely enumerated and it is not known whether pathology arises from the expression of physiologic targets at abnormal levels or from the pathologic response of new target genes that are not normally regulated by MYC. Regardless of which, available evidence indicates that the level of MYC expression is an important determinant of MYC biology. The c-myc promoter has architectural and functional features that contribute to uniform expression and help to prevent or mitigate conditions that might otherwise create noisy expression. Those features include the use of an expanded proximal promoter, the averaging of input from dozens of transcription factors, and real-time feedback using the supercoil-deformable Far UpStream Element (FUSE) as physical sensor of ongoing transcriptional activity, and the FUSE binding protein (FBP) as well as the FBP interacting repressor (FIR) as effectors to enforce normal transcription from the c-myc promoter.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.21 no.3
• /
• pp.314-318
• /
• 1992

The sarcoma 180 cells were treated with ursolic acid which was previously extracted from leaves of Eriobotrya japonica Lindy (Rosaceae) and identified as a potent anticarinogenic agent. Suppressing effects of the compounds with testing changes in selected oncogenes expression were examined by using the northern hybridization method. Ursolic acid significantly suppressed c-myc oncogene expression. However, c-ha-ras oncogene expression was lowered slightly with the ursolic acid treatment. Therefore, it was concluded that preproven anticarcinogenic effects of ursolic acid should be partly ascribed to the modified oncogenic expression.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.6
• /
• pp.691-697
• /
• 1997

The mechanisms underlying opiate tolerance and dependence are not fully understood. We used human neuroblastoma SH-SY5Y cells as a model system for studying effects of morphine tolerance and withdrawal on c-myc induction and cAMP levels. It has been reported that regulation of c-fos by acute and chronic morphine withdrawal is mediated through alterations in CREB transcription factor. In this study, we examined the effects of morphine tolerance on c-myc expression and cAMP concentrations. The activation of opiate receptors by an acute morphine administration resulted in an increase in c-myc mRNA and a decrease in cAMP concentrations in a dose-dependent manner $(5,\;10,\;15,\;and\;20\;{\mu}M)$. On the other hand, the chronic treatment of morphine $(10\;{\mu}M\;for\;six\;days)$ did not induce the elevated expression of c-myc mRNA. The c-myc expression was slightly inhibited in comparison with that of the acute morphine response. However, cAMP concentrations were increased with regard to morphine withdrawal response. These results suggest that the alterations in c-myc expression might imply a significant opiate regulation relating to morphine tolerance. This observation differs from increased expression of c-fos via regulation of cAMP pathway.

• Journal of Life Science
• /
• v.10 no.6
• /
• pp.621-629
• /
• 2000

Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA “cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT. CPT.

• Journal of Life Science
• /
• v.5 no.3
• /
• pp.105-116
• /
• 1995

To investigate genomic changes in c-myc gene by a chemical carcinogen, human lymphoblast NC-37 cells were exposed to benzo(a)pyrene(BP) and dimethylbenzanthracene(DMBA), and the c-myc gene expression was evaluated by Northern and Southern blot hybridization techniques. The results are as follows: When the genomic DNA of NC-37 cells exposed to several concentrations(1.25, 2.5 and 5ug/ml) of BP concentration. However, the c-myc gene was most significantly enhanced with 2.5ug/ml of BP. The expressions of c-myc gene in NC-37 cells was stimulated by BP and DMBA. Addition of TPA reduced the gene expression BP-treated cells, whereas it enhanced the gene expression in DMBA-treated cells. The expression of c-H-ras gene was slightly increased by treatment with BP and DMBA alone and in combination with TPA, however the magnitude of increase was not significantly different between each other. The expressions of c-myc c-H-ras genes in Burkitt's lymphoma cells were greater than those in NC-37 cells. When the DNA extracted from NC-37 cells exposed to various concentrations of BP were amplified by polymerase chain reaction using a primer set containing c-myc exon I, the amplified products were of the same size in all groups. To evaluate the BP toxicity in E.coli to which human c-myc gene-cloned pBR322 vector was inserted, Southern blot hybridization was conducted on c-myc genes digested with EcoRI/HindIII and Smal/Xbal restriction enzymes, and observing that in 2 ug/ml BP-treated cells a 3.5kb fragment was generated in addition to 1.3kb fragment which can be observed in normal cells. Direct nucleotide sequence analysis of polymerase chain reaction products showed a mutation of G$\longrightarrow$A transition at the Smal recognition site.

• Journal of Yeungnam Medical Science
• /
• v.14 no.1
• /
• pp.67-76
• /
• 1997

The occurrence of multidrug resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. In this study The gene expressions of multidrug resistance-associated protein (MRP), c-myc and c-fos were investigated in L1210 cells. Adriamycin- or vincristine-resistant L1210 cells, L1210AdR or L1210VcR, respectively, has been identified to overexpression of mdr1 gene. The expression leve of MRP gene in L1210AdR and L1210Cis was more decreased than that in L1210 cells. The c-myc and c-fos genes were expressed both in L1210 and resistant sublines. In L1210AdR, the expressions level of c-myc and c-fos genes were decreased than in L1210. However, in L1210VcR and L1210Cis, c-myc and c-fosgene expressionwere rather increased than L1210. These results suggested that MRP does not contribute in resistance of drug-resistant L1210 cells and there is no relations between MRP and mdr1 gene expression. The expression of c-myc and c-fos gene may be changed during transformation of L1210 to drug-resistant sublines.

• The Korean Journal of Zoology
• /
• v.38 no.2
• /
• pp.196-203
• /
• 1995

The c-myc proto-oncogene, one of the immediately earlY genes, is expressed in various mammalian cell types and heavily involved in the regulation of cell proliferation and differentiation. To determine endogeneous expression pattern of c-myc gene in preimpBantation mouse embwos, we employed a reverse transcription coupled to polvrnerase chain reaction (RT-PCR). Transcript of c-myc was detected at fertilized embryos as a maternal transcript. At the early two-cell stave, transcript of c-myc gene was hardly detected, bu, appeared at late two-cell embryos as a zygotic transcript. The level of c-myc expresion was increased at later stases and peaked at blastocvst stage. To examine the functional role of promoter region for c-myc gene transcription, we fused the 5'upstream region (1.8 kb) including econ 1 of c-myc genomic DNA with E. coli lacE gene fnamed as pcMYC-laczl. pcMYC-lacZ was microiniected into the pronscleus of mouse one-cell embryovs, and p·salactosidase activity was determined tv histochemical staining with X-gal at different stases. f-galactosidase activity was detected only at blastocyst, but not at the earlier stage embryos. This result indicates that c-myc gene is transcriptionallv active during mouse preimplantation development.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2000.11a
• /
• pp.45-67
• /
• 2000

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a mutagenic and carcinogenic heterocyclic amino found in cooked meat. The in vivo mutagenicity and hepatocarcinogenicity of MeIQx were examined in mice harboring the lacZ mutation reporter gene ($Muta^{TM}$ Mice) and bitransgenic mice over-expressing the c-myc oncogene. C57B1/$\lambda$lacZ and bitransgenic c-myc (albumin promoter)/$\lambda$lacZ mice were bred and weaned onto an AIN-76 based diet containing $0.06\%$ (w/w) MeIQx or onto control diet. After 30 weeks on diet, only male bitransgenic mice on MeIQx developed hepatocellular carcinoma ($100\%$ incidence) indicating that there was synergism between c-myc over-expression and MeIQx. By 40 weeks, hepatic tumor incidence was $100\%$ ($17\%$) and $44\%$ ($0\%$) in male c-myc/$\lambda$lacZ and C57B1/$\lambda$lacZ mice given MeIQx (or control) diet, respectively, indicating that either MeIQx or c-myc over-expression alone eventually induced hepatic tumors. At either time point, mutant frequency in the lacZ gene was at least 40-fold higher in MeIQx-treated mice than in control mice of either strain. These findings suggest that MeIQx-induced hepatocarcinogenesis is associated with MeIQx-induced mutations. Elevated mutant frequency in MeIQx-treated mice also occurred concomitant with the formation of MeIQx-guanine adducts as detected by the $^{32}P$-postlabeling assay. Irrespective of strain or diet, sequence analysis of the lacZ mutants from male mouse liver showed that the principal sequence alteration was a single guanine-base substitution. Adenine mutations, however, were detected only in animals on control diet. MeIQx-fed mice harboring the c-myc oncogene showed a l.4-2.6-fold higher mutant frequency in the lacZ gene than mice not carrying the transgene. Although there was a trend toward higher adduct levels in c-myc mice, MeIQx-DNA adduct levels were not significantly different between c-myc/$\lambda$lacZ and C57B1/$\lambda$lacZ mice after 30 weeks on diet. Thus, it appeared that factors in addition to MeIQx-DNA adduct levels, such as the enhance rate of proliferation associated with c-myc over-expression, may have accounted for a higher mutant frequency in c-myc mice. In the control diet groups, the lacZ mutant frequency was significantly higher in c-myc/$\lambda$lacZ mice than in 057B1/$\lambda$1acZ mice. The findings are consistent with the notion that c-myc over-expression is associated with an increase in mutagenesis. The mechanism for the synergistic effects of c-myc over-expression on MeIQx hepatocarcinogenicity appears to involve an enhancement of MeIQx-induced mutations.

• Journal of the Korea Convergence Society
• /
• v.10 no.6
• /
• pp.65-71
• /
• 2019

The propose of this study has been conducted to examine expression of c-Myc and Thymosin-${\beta}4$ in liver cirrhosis model from liver fibrosis and For the method of study, the experiment was conducted in 2 groups; liver cirrhosis model experiment group due to liver fibrosis and control group with distilled water. This study outcome showed that liver cirrhosis model experiment group had significantly higher expression of c-Myc and Thymosin-${\beta}4$. with changes to hepatic tissue of special staining and electron microscopy. In conclusion, in clinical tests regarding liver function, molecular evaluation of c-Myc and Thymosin-${\beta}4$ and their expression along with serological change and histological assessment can be utilized as a reference for diagnosing liver disease for prevention and diagnosis of the disease, Based on this research in the future, we will carry out an in-depth study by adding the types of experimental groups and related genes.