Detection of Proto-Oncogenes in the Genome of the Amphibian Ambystoma mexicanum

Chung, Young-Lan 梨花女子大學校 韓國生活科學硏究院 1993 韓國生活科學硏究院 論叢 Vol.52 No.-

Amphibian Ambystoma mexicanum genome was probed by Southern blot analysis for the presence of sequences homologous to nine mammalian or avian oncogences. Four genes representing two oncogene families exhibited positive signals with specific axolotl DNA restriction fragments including v-abl, v-erbB, v-fps and v-Ha-ras. v-abl gave the strongest hybridization and the signal remained positive in higher stringency wash condition. This study shows the relative conservation of these poto-oncogenes during evolution. Using positive probes, axolotl proto-oncogenes can be cloned and this study opens the possibility of studying the role of poto-oncogenes during axolotl limb regeneration. 양서류 Axolotl의 다리 재생에 있어서 세포분열과 분화를 조절하는 proto-oncogene의 발현을 연구하는 것은 생물학적으로 아주 의미 있는 일이다. 본 연구는 위의 연구를 수행하기 위하여 양서류 Ambystoma mexicanum의 게놈에 포유류나 조류의 oncogene과 비슷한 염기서열을 가진 유전자가 있는지 탐지하기 위해 Southern방법으로 분석하였다. 두 oncogene 계열에 속하는 4개의 유전자가 제한효소로 처리한 Axolotl의 게놈의 유전자 조각에 각각 결합하였다. Protein kinase oncogene family에 속하는 abl, fps와 erb B 유전자가 양성 시그날을 보였다. 또한 ras family에 속하는 H-ras가 특이한 Axolotl DNA 조각에 결합하여 양성 signal을 보였다. 본 연구로 singnal을 보인 4개의 Proto-oncogene들은 진화의 과정에서 그 염기서열을 보존하고 있음을 알 수 있다. 본 실험에서 양성 시그날을 보인 탐침 DNA들을 이용하여 그에 해당하는 Axolotl proto-oncogene을 클론 할 수 있다. 또한 이들 탐침 DNA는 양서류의 다리 재생 중 proto-oncogene의 발현 양성과 그 조절에 대한 연구를 가능하게 하였다.

결장 및 직장암에서 c-myc, c-erb B₂ 및 c-Ha ras 암유전자의 발현

김영진,박창수 대한대장항문학회 1993 Annals of Coloproctolgy Vol.9 No.4

Inhibition of Oncogenes Affects the Expression of NKG2D Ligands in Cancer Cells

Woong Heo(허웅),Young Shin Lee(이영신),Jaeho Bae(배재호) 한국생명과학회 2013 생명과학회지 Vol.23 No.10

자연살상세포(NK cells)은 림프구계의 세포로서 외부 침임 병원균을 막고 체내 형질변환세포를 제거하는데 참여하고 있다. 이러한 자연살상세포의 활성은 특정한 항원이 필요 없고 활성화 신호와 억제성 신호의 균형에 의해 조절되고 있다. 자연살상세포의 중요한 활성화 신호 중의 하나는 NKG2D 수용체를 통한 것인데, 이 NKG2D 수용체를 통해 자연살상세포는 암세포에 있는 NKG2D 리간드를 인식할 수 있다. 지금까지 인간에서는 여덟개의 NKG2D 리간드가 밝혀져 있고 이러한 리간드의 발현은 다양한 기전을 엄격하게 조절되고 있다. 암세포는 암유전자(oncogenes)에 의해 세포내 다양한 유전자의 발현이 정상세포와 확연히 달라지는데, 이러한 암유전자에 의해서 NKG2D 리간드의 발현이 영향을 받을 것으로 생각되어 진다. 이 연구는 인간의 암세포에서 가장 자주 발현되는 세가지 암유전자 k-ras와 c-myc, wnt의 억제를 통해 NKG2D 리간드의 발현이 어떻게 변화되는 지를 알아보았다. k-ras와 c-myc의 억제는 NKG2D 리간드의 발현을 효과적을 증가시켰고 암세포가 자연살상세포에 더욱 잘 죽게 변화되었다. 그러나 wnt 억제는 MICA와 ULBP1의 전사를 감소시켰다. wnt 억제에 의한 NKG2D 리간드의 전사 억제에도 불구하고 세포막의 단백질 발현은 변하지 않아서 암세포의 자연살상세포에 대한 감수성은 별다른 변화를 보이지 않았다. 따라서 k-ras와 c-myc, wnt 억제는 각각 다른 반응을 보였으며 최종적인 자연살상세포에 대한 감수성은 NKG2D 리간드의 세포표면단백질 발현정도에 의해 결정됨을 알 수 있었다. NK cells are lymphoid immune cells that participate in innate immunity to protect against foreign pathogens and transforming cells. It is known that the activity of NK cells is regulated by a balance between activating and inhibitory signals rather than specific antigens. One important activating signal is mediated by the NKG2D receptor, which recognizes NKG2D ligands on cancer cells. Therefore, tumor cells that express sufficient amounts of NKG2D ligands could be eliminated by NKD2D+ cells, including NK cells. Oncogenes drive tumor cells to apoptosis resistant and uncontrolled proliferation by altered expression of many critical genes. Therefore, the expression of NKG2D ligands may be affected by oncogenes. This study focused on increasing the susceptibility of cancer cells to NK cells by regulating the expression of NKG2D ligands influenced by three oncogenes: k-ras, wnt, and c-myc. We demonstrated that inhibition of k-ras and c-myc increased the expression of NKG2D ligands and enhanced the susceptibility of cancer cells to NK cells. On the contrary, inhibition of the wnt pathway decreased MICA and ULBP1 transcripts. Although the decreased transcription of NKG2D ligands by inhibition of the wnt pathway, surface proteins of NKG2D ligands were not changed, and the susceptibility of HCT-116 cells was unaffected. The results demonstrate that the transcription of NKG2D ligands are regulated deferentially by the k-ras, c-myc, and wnt pathways and that the cytotoxicity of NK cells solely depends on the amount of surface NKG2D ligands.

Gene Regulatory Network Analysis for Triple-Negative Breast Neoplasms by Using Gene Expression Data

정희찬,김성환,이정훈,김주한,한성원 한국유방암학회 2017 Journal of breast cancer Vol.20 No.3

Purpose: To better identify the physiology of triple-negative breast neoplasm (TNBN), we analyzed the TNBN gene regulatory network using gene expression data. Methods: We collected TNBN gene expression data from The Cancer Genome Atlas to construct a TNBN gene regulatory network using least absolute shrinkage and selection operator regression. In addition, we constructed a triple-positive breast neoplasm (TPBN) network for comparison. Furthermore, survival analysis based on gene expression levels and differentially expressed gene (DEG) analysis were carried out to support and compare the network analysis results, respectively. Results: The TNBN gene regulatory network, which followed a power-law distribution, had 10,237 vertices and 17,773 edges, with an average vertex-to-vertex distance of 8.6. The genes ZDHHC20 and RAPGEF6 were identified by centrality analysis to be important vertices. However, in the DEG analysis, we could not find meaningful fold changes in ZDHHC20 and RAPGEF6 between the TPBN and TNBN gene expression data. In the multivariate survival analysis, the hazard ratio for ZDHHC20 and RAPGEF6 was 1.677 (1.192–2.357) and 1.676 (1.222–2.299), respectively. Conclusion: Our TNBN gene regulatory network was a scale-free one, which means that the network would be easily destroyed if the hub vertices were attacked. Thus, it is important to identify the hub vertices in the network analysis. In the TNBN gene regulatory network, ZDHHC20 and RAPGEF6 were found to be oncogenes. Further study of these genes could help to reveal a novel method for treating TNBN in the future.

Replicating poxviruses for human cancer therapy

김만복 한국미생물학회 2015 The journal of microbiology Vol.53 No.4

Naturally occurring oncolytic viruses are live, replicationproficientviruses that specifically infect human cancer cellswhile sparing normal cell counterparts. Since the eradicationof smallpox in the 1970s with the aid of vaccinia viruses,the vaccinia viruses and other genera of poxviruses haveshown various degrees of safety and efficacy in pre-clinicalor clinical application for human anti-cancer therapeutics. Furthermore, we have recently discovered that cellular tumorsuppressor genes are important in determining poxviraloncolytic tropism. Since carcinogenesis is a multi-stepprocess involving accumulation of both oncogene and tumorsuppressor gene abnormalities, it is interesting that poxviruscan exploit abnormal cellular tumor suppressor signalingfor its oncolytic specificity and efficacy. Many tumor suppressorgenes such as p53, ATM, and RB are known to playimportant roles in genomic fidelity/maintenance. Thus, tumorsuppressor gene abnormality could affect host genomicintegrity and likely disrupt intact antiviral networks due toaccumulation of genetic defects, which would in turn resultin oncolytic virus susceptibility. This review outlines the characteristicsof oncolytic poxvirus strains, including vaccinia,myxoma, and squirrelpox virus, recent progress in elucidatingthe molecular connection between oncogene/tumorsuppressor gene abnormalities and poxviral oncolytic tropism,and the associated preclinical/clinical implications. I wouldalso like to propose future directions in the utility of poxvirusesfor oncolytic virotherapy.

Annotation of Genes Having Candidate Somatic Mutations in Acute Myeloid Leukemia with Whole-Exome Sequencing Using Concept Lattice Analysis

이계화,임재현,김주한 한국유전체학회 2013 Genomics & informatics Vol.11 No.1

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.

Annotation of Genes Having Candidate Somatic Mutations in Acute Myeloid Leukemia with Whole-Exome Sequencing Using Concept Lattice Analysis

Lee, Kye Hwa,Lim, Jae Hyeun,Kim, Ju Han Korea Genome Organization 2013 Genomics & informatics Vol.11 No.1

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.

Annotation of Genes Having Candidate Somatic Mutations in Acute Myeloid Leukemia with Whole-Exome Sequencing Using Concept Lattice Analysis

이계화,임재현,김주한 한국유전체학회 2013 Genomics & informatics Vol.11 No.2

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.

건선 조직에서의 c - fos 및 c - myc 암유전자 발현 증가

최윤애(Yoon Yae Choi),이규석(Kyu Suk Lee) 대한피부과학회 1991 대한피부과학회지 Vol.29 No.3

The expression of the c-fos and c-myc oncogenes was investigated by dot blot analysis of total RNA extracted from biopsies of normal skin and psoriatic lesions. Densitometric analysis revealed 6.3 fold and 8.6 fold evevation respectively of c-fos and c-myc oncogenes mRNA levels in severe psoriasis compared to normal skin, and 1.5 fold and 1.6 fold elevation respectively of c-fos and c-myc oncogenes mRNA levels in mild psoriasis compared to normal skin. The ratio of c-fos/c-myc transcripts in normal skin and mild psoriasis was constant compared to that in severe psoriasis. The maintenance of a constant ratio of c-fos/c-myc is believed to be closely related to ordered cell growth and the ratio of c-fos/c-myc transcripts in severe psoriasis suggests a disordered pattern of cellular differentiation. We be1ieve that overexpression of these oncogenes is related to the pathogenesis of psoriatic epidermal hyperplasia. (Kor J Dermatol 29(3): 331 336,1991)

Prognostically Significant Fusion Oncogenes in Pakistani Patients with Adult Acute Lymphoblastic Leukemia and their Association with Disease Biology and Outcome

Sabir, Noreen,Iqbal, Zafar,Aleem, Aamer,Awan, Tashfeen,Naeem, Tahir,Asad, Sultan,Tahir, Ammara H,Absar, Muhammad,Hasanato, Rana MW,Basit, Sulman,Chishti, Muhammad Azhar,Ul-Haque, Muhammad Faiyaz,Khali Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than $50{\times}10^9/l$. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.