• Journal of Genetic Medicine
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• 제1권1호
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• pp.45-50
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• 1997

Neuroblastoma, a pediatric malignant neoplasm of neural crest origin, has a wide range of clinical virulence. The mechanisms contributing to the development of neuroblastomas are largely unclear, but non-random chromosomal changes identified over the past years suggest the involvement of genetic alterations. Amplification of the human N-myc proto-oncogene is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions (HSRs) of aggressively growing neuroblastomas. N-myc maps to chromosome 2 band 24, but HSR have never been observed at this band, suggesting transposition of N-myc during amplification. We have constructed and analyzed the region-specific painting probe for HSR in neuroblastoma IMR-32 to determine the derivative chromosomes. Microdissection was performed on HSR using an inverted microscope with the help of microglass needles and an micromanipulator. We pretreated the microdissected fragments with Topoisomerase I which catalyzes the relaxation of supercolled DNA, and performed two initial rounds of DNA synthesis with T7 DNA polymerase followed by conventional PCR to enable the reliable preparation of Fluorescent in situ hybridization probe from a single microdissected chromosome. With this method, it was possible to construct the region-specific painting probe for HSR. The probe hybridized specifically to the HSRs of IMR-32, and to 2p24, 2p13 of normal chromosome. Our results suggest there was coamplification of N-myc together with DNA of the chromosome 2p24 and 2p13. Moreover, the fluorescent signals for the amplified chromosomal regions in IMR-32 cells were also easily recognized at a Thus this painting probe can be applied to detect the similar amplification of N-myc in neuroblastoma tissue, and the probe pool for HSR may be used to identify the cancer-relevant genes.

• Journal of Yeungnam Medical Science
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• 제12권2호
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• pp.210-225
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• 1995

1983년 6월부터 1993년 5월까지 10년간 영남대학교 의과대학 부속병원에서 결장 및 직장암으로 절제되어, 병리조직학적으로 결장 및 직장암으로 확진된 예 중, 파라핀 포매조직의 상태가 양호한 선암종 67례를 대상으로 하여 면역조직화학적 방법을 이용해서 대장암에서의 $p62^{c-myc}$과 $p21^{ras}$의 발현양상을 검색함으로써 종양유전자 산물과 대장암의 유형, 분화도 및 Dukes stage에 따른 연관성 유무를 관찰한 바 다음과 같은 결과를 얻었다. 결장 및 직장암에서 $p62^{c-myc}$ 발현은 직장암에서 더 많았으며 그 양상은 주로 미만성 반응이 많았고(p<0.05), $p21^{ras}$ 발현은 여자에서 더 많았다(p<0.05). 분화도에 따라서는 고분화 선암종에서 미만성으로 나타났고 강양성 반응의 경향을 보였다. 수정된 Dukes stage와 두 종양유전자 산물의 발현은 비교적 초기에 미만성으로 나타났다. 종양유전자 $p62^{c-myc}$의 발현은 전이된 림프절에서 원발병소보다 미만성, 강양성으로 더 많이 관찰 되었고, $p21^{ras}$의 발현은 원발병소에서 더 양성반응이 많았고 주로 미만성, 강양성으로 나타나는 경향이었다. 환자의 나이, 종양의 육안소견과는 통계학적 유의성이 없었다. 이상의 연구를 요약하면 종양유전자 산물 $p62^{c-myc}$과 $p21^{ras}$의 발현은 대장암 초기 및 고분화 선암종에서 더 많이 나타나는 것으로 생각되었고 환자의 나이, 종양의 육안소견과는 관련이 없는 것으로 사료되었다.

• 대한수의학회지
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• 제40권1호
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• pp.117-129
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• 2000

This study was carried out to examine proliferative activity and expression of c-myc oncoprotein and p2lras in normal and preneoplastic rat livers induced by an in vivo mid-term chemical carcinogenesis assay. Sixty, six-week-old male specific pathogen free Sprague-Dawley male rats were randomly divided into five groups. Group I was received a single intraperitoneal(IP) dose(200mg/kg) of diethylnitrosamine(DEN). Group 2(10 rats) was operated partial hepatectomy(PH) and Group 3 was received IP(200mg/kg) DEN, fed two weeks later with 500ppm of phenobarbital(PB). Group 4 was received IP(200mg/kg) DEN, fed two weeks later 500ppm(PB) and PH at week 3 after the onset of experiment. While group 5(20 rats) was not treated and used as a control group. All the rats were sacrificed at age 14 weeks except 10 rats from group 5 were sacrificed at the onset of experiment. Livers of all rats were examined for 5-bromo-2'-deoxyuridine(BrdU) incoporation, proliferating cell nuclear antigen(PCNA), silver-binding nucleolar organizer regions(AgNORs) counts per nucleus and expression of c-myc oncoprotein and p21ras. Both the number and area of the preneoplastic lesions were significantly(p<0.01) compared to other groups. A significant(p<0.01) increase in immunoreactive cells were detected in preneoplastic hepatocytes in Groups 3 and 4 by PCNA and BrdU immunohistochemical stain. The number of the positive cells were significantly(p<0.05) lower in normal 14-week-old rats than those of 6-week-old rats. The results showed that proliferative activity of the hepatocytes was increased by treatment with DEN, PH and PB. Meanwhile, AgNORs counts per nucleus were significantly(p<0.05) increased in the preneoplastic hepatocytes of rats in both groups 3 and 4. The expression of c-myc oncoprotein and p21ras were more readily localized within the hepatic preneoplastic lesions such as hyperplastic nodules. Especially, group 4 showed significantly (p<0.05) overexpressed levels compared to groups 1 and 3. These findings suggest that PCNA, BrdU and AgNORs are significantly increased and c-myc oncoprotein and p21ras are significantly overexpressed in hepatic preneoplastic lesions induced by mid-term carcinogenesis. So these parameters can be an effective markers for hepatic prencoplastic lesions.

• 동서간호학연구지
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• 제29권2호
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• pp.161-171
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• 2023

Purpose: The purpose of this study is to verify the effectiveness of the Environmental Hazards Exposure Prevention Program for Mothers with Young Child (EHEPP-MYC) and to provide basic data for environmental health projects in the community. Methods: EHEPP-MYC was developed based on the protection motivation theory. A quasi-experimental design was applied to evaluate the effectiveness of the program. The number of study participants was 30 in the experimental group and 31 in the control group. The intervention applied to the experimental group consisted of lectures as the main method, current affairs programs, discussions, booklets, animations, and practical training. The program was held twice a week for a total of 4 sessions of 60 minutes each. The effect of applying the program was measured three times through surveys (before, immediately after, and two weeks after the intervention) and analyzed through repeated measures ANOVA. Results: The EHEPP-MYC had significant effects on preventive behavior, perceived severity, perceived vulnerability, self-efficacy, response efficacy, and response costs at three time points. Conclusion: EHEPP-MYC has been shown to be effective in promoting environmental hazards prevention behaviors among mothers of young child. EHEPP-MYC can be used as baseline data for projects developing programs to prevent exposure to environmental hazards and improve the environmental health of communities.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7997-8002
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• 2015

Gene amplification is an important mechanism in the development and progression of cancer. Currently, gene amplification status is generally determined by in situ hybridization (ISH). Multiplex ligation-dependent probe amplification (MLPA) is a PCR-based method that allows copy number detection of up to 50 nucleic acid sequences in one reaction. The aim of the present study was to compare results for HER2, CCND1, MYC and ESR1 gene amplification detected by MLPA with fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) as clinically approved methods. Tissue samples of 170 invasive breast cancers were collected. All were ER positive. Tissue samples had previously been tested for HER2 using immunohistochemistry. Amplification of the selected genes were assessed using MLPA, FISH and CISH and results were compared. HER2 MLPA and ISH results were also compared with HER2 immunohistochemistry (IHC) which detects protein overexpression. Amplification of HER2, CCND1, MYC and ESR1 by MLPA were found in 9%, 19%, 20% and 2% of samples, respectively. Amplification of HER2, CCND1, MYC and ESR1 by FISH was noted in 7%, 16%, 16% and 1% of samples, respectively. A high level of concordance was found between MLPA/FISH (HER2: 88%, CCND1: 88%, MYC: 86%, ESR1: 92%) and MLPA/CISH (HER2: 84%). Of all IHC 3+ cases, 91% were amplified by MLPA. In IHC 2+ group, 31% were MLPA amplified. In IHC 1+ group, 2% were MLPA amplified. None of the IHC 0 cases were amplified by MLPA. Our results indicate that there is a good correlation between MLPA, IHC and ISH results. Therefore, MLPA can serve as an alternative to ISH for detection of gene amplification.

• Asian-Australasian Journal of Animal Sciences
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• 제28권11호
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• pp.1545-1550
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• 2015

c-MYC (v-myelocytomatosis viral oncogene homologue) is a transcription factor that plays important role in many biological process including cell growth and differentiation, such as myogenesis and adipogenesis. In this study, we aimed to detect MYC gene polymorphisms, their genotype frequencies and to determine associations between these polymorphisms and meat quality traits in Berkshire pigs. We identified a single nucleotide polymorphism (SNP) in intron 2 of MYC gene by Sanger sequencing, i.e., g.3350G>C (rs321898326), that is only found in Berkshire pigs, but not in other breeds including Duroc, Landrace, and Yorkshire pigs that were used in this study. Genotypes of total 378 Berkshire pigs (138 sows and 240 boars) were determined using Hha I restriction enzyme digestion after polymerase chain reaction. Observed allele frequencies of GG, GC, and CC genotypes were 0.399, 0.508, and 0.093 respectively. Statistical analysis indicated that the g.3350G>C polymorphism was significantly associated with $pH_{45min}$ and cooking loss (p<0.05), suggesting that g.3350G>C SNP can be used for pre-selection of $pH_{45min}$ and cooking loss traits in Berkshire pigs.

• Toxicological Research
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• 제20권4호
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• pp.307-313
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• 2004

The present study was undertaken to investigate the effects of mistletoe (Viscum album var. coloratum) growing on Carpinus laxiflora BL. on proliferation and differentiation of HL-60 acute promyelocytic leukemia cells. Aqueous extract and its $(NH_2)_2SO_4$ saturated fractions of the mistletoe exhibited potent anti-proliferation activity against HL-60 cells. Moreover, when HL-60 cells were treated with 0~30% and 30～70% $(NH_2)_2SO_4$ saturated fractions of the mistletoe, HL-60 expressed CD 66b or CD 14 cell surface antigens and showed activity to reduce nitroblue tetrazolium, indicating that mistletoe induces the differentiation of HL-60 into granulocytes or monocytes. To understand how mistletoe induces the differentiation, we investigated the expression of molecules for modulating the proliferation and differentiation of leukemia cells, such as c-Myc and myeloblastin. The 0~30% $(NH_2)_2SO_4$ saturated fraction of the mistletoe reduced the mRNA levels of c-Myc and myeloblastin in a time-dependent manner. The results indicate that the mistletoe induces the differentiation of HL-60 cells via the decrease of c-Myc and myeloblastin expressions. Thus, it is suggested that mistletoe has a therapeutic potential for the treatment of acute promyelocytic leukemia.

• Molecules and Cells
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• 제43권2호
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• pp.176-181
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• 2020

The RUNX transcription factors serve as master regulators of development and are frequently dysregulated in human cancers. Among the three family members, RUNX3 is the least studied, and has long been considered to be a tumor-suppressor gene in human cancers. This idea is mainly based on the observation that RUNX3 is inactivated by genetic/epigenetic alterations or protein mislocalization during the initiation of tumorigenesis. Recently, this paradigm has been challenged, as several lines of evidence have shown that RUNX3 is upregulated over the course of tumor development. Resolving this paradox and understanding how a single gene can exhibit both oncogenic and tumor-suppressive properties is essential for successful drug targeting of RUNX. We propose a simple explanation for the duality of RUNX3: p53 status. In this model, p53 deficiency causes RUNX3 to become an oncogene, resulting in aberrant upregulation of MYC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3681-3685
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• 2012

Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the $TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer.

• Toxicological Research
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• 제27권4호
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• pp.253-259
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• 2011

Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.