• 한국동물학회지
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• 제38권4호
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• pp.550-556
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• 1995

c-myc proto-oncogene은 여러 세포들의 분화와 형질전화에 뿐만 아니라 정상세포의 분열조절에도 관여한다고 알려져왔다. 특히 생쥐의 초기배아에서 c-myc mRNA가 발현되고 antisense c-myc oligomer의 미세주입에 의해 배발생이 억제된다는 연구결과는 c-myc이 초기배아의 발생 및 분열에 관여하는 것을 시사한다. 그러나 최근까지 초기배아에 존재하는 c-myc promoter의 기능적 활성화에 관한 연구는 미진하였다. 이를 위하여, c-myc promoter와 대장균의 lacZ 유전자를 결합시킨 두 종류의 vector(pcmyc-Gall, pcmyc-Ga12)를 만들어 수정란의 전핵에 미세주입한 후, 배 발생에 따른 c-myc promoter의 활성화를 lacZ 유전자의 산물인 $\beta$-galactosidase 에 의한 X-gal 염색으로 조사하였다. 미세주입된 초기 배아는 2세포기 배아를 포함하는 여러 발생단계에서 $\beta$-galactosidase 의 활성을 보였다. 이는 c-myc 유전자가 배아의 게놈유전자로부터 발현되며, 또한 궁극적으로 초기 배아의 발생과정에 중요한 역할을 하고 있음을 시사하고 있다.

• Molecules and Cells
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• 제20권2호
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• pp.157-166
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• 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.

• 한국식품영양과학회지
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• 제21권3호
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• pp.314-318
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• 1992

비파엽에서 분리동정한 활성성분인 울솔레산을 sarcoma 180 cells에 처리하여 c-myc과 c-Ha-ras 암유전자 발현에 있어서 변화를 조사하였다. 그 결과 c-myc 유전자의 발현에서는 뚜렸한 감소가 관찰되었으나 c-Ha-ras 유전자 발현은 대조군과 거의 차이가 없었다. Cell proliferation에 중요한 역할을 하는 것으로 추측되고 있는 c-myc 유전자 발현의 감소는 지금까지 보고된 그 물질의 antipromotional effect와 관계있는 것으로 보여진다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.691-697
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• 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.

• 생명과학회지
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• 제10권6호
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• pp.621-629
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• 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.

• 생명과학회지
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• 제5권3호
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• pp.105-116
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• 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
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• 제14권1호
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• pp.67-76
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• 1997

항암제에 대한 내성은 내인성 또는 획득한 내성 모두가 암의 치료에 장애가 된다. P-당단백질을 encode하고있는 mdr1 유전자의 발현이 항암제에 대해 내성을 가지고 있는 암세포에서 많이 관찰되고 있으며, 최근에는 시험관적으로 항암제에 대한 내성이 유도된 암세포주들에서 mdr1 유전자가 발현되지 않는 암세포들이 보고되고 있다. 다제내성에 관계하는 또 하나의 유전자인 MRP 발현정도를 L1210세포와 내성인 L1210변이주들에서 조사하였으며, c-myc과 c-fos 유전자의 발현변화를 관찰하였다. RT-PCR을 시행하여 L1210, L1210AdR, L1210VcR에서 MRP 유전자발현을 확인하였으며, Northern hybridization한 결과 L1210세포에 비하여 L1210AdR은 유전자 발현이 40% 정도 감소하였으며, L12l0Cis는 90% 정도의 유전자 발현감소가 관찰되었다. c-myc과 c-fos유전자의 Northern hybridization한 결과 L1210에 비하여 L1210AdR은 발현감소가 나타났으나, L1210VcR과 L1210Cis의 경우는 오히려 발현증가가 관찰되었다.

• 한국동물학회지
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• 제38권2호
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• pp.196-203
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• 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.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2000년도 국제심포지움 및 추계학술대회
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• pp.45-67
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• 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.

• 한국융합학회논문지
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• 제10권6호
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• pp.65-71
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• 2019

이 연구의 목적은 간 섬유화로 인한 간경변 모델에서 c-Myc과, Thymosin-${\beta}4$ 유전자의 발현을 알아 보고자 실시하였으며 연구 방법은 2군으로 나누어 섬유화로 인한 간경변 모델 실험군과 증류수를 이용한 대조군으로 분류 한 후 실험을 하였다. 본 연구를 통한 결과는 간경변 모델 실험군은 대조군에 비하여 c-Myc과 Thymosin-${\beta}4$의 발현이 증가 되는 것을 뚜렷하게 알 수 있었고, 전자현미경적 검경 외에 여러 특수 염색을 통하여 간조직의 변화를 관찰 할 수 있었다. 결론적으로 기존 간기능 검사 관련 임상검사에서 질환 예방과 질환 판정 시 혈청학적 변화와 조직학적인 검사와 더불어 c-Myc과 Thymosin-${\beta}4$의 분자 기법을 통한 유전자의 발현 상태를 확인함으로써 간 질환 판정에 기여 할 수 있을 것으로 사료 되며, 향후 이 연구를 기반으로 실험군의 종류와 관련 유전자를 추가 하여 심도 있는 연구를 진행할 예정이다.