• Korean Journal of Poultry Science
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• v.34 no.1
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• pp.57-76
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• 2007

Marek's disease (MD) is caused by a ubiquitous, lymphotropic alphaherpesvirus, MD virus (MDV). MD has been a major concern in the poultry industry due to the emergence of increasingly virulent strains over the last few decades that were isolated in the face of comprehensive vaccination. MD is characterized by a variety of clinical signs, amongst them neurological symptoms, chronic wasting, and most notably the development of multiple lymphomas that manifest as solid tumors in the viscera and musculature. Much work has been devoted to study MD-induced oncogenesis and genes involved in this process. Among the many genes encoded by MDV, a number have recently been shown to affect the development of tumors in chickens, one protein directly causing transformation of cells (Meq) and another being involved in maintaining transformed cells (vTR). Other MDV gene products modulate and are involved in early lytic in vivo replication, thereby increasing the chance of transformation occurring. In this review, specific genes encoded by MDV that are involved in the initiation and/or maintenance of transformation were briefly summarized, and limits of current vaccination and new control strategies against MD, particularly how modem molecular biological methods may be used to improve strategies to combat the disease in the future, were discussed.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.49-53
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• 2013

A number of naturally-occurring or synthetic chemicals have been reported to exhibit prostate chemopreventive effects. Synthetic $5{\alpha}$-reductase (5-AR) inhibitors, e.g. finasteride and durasteride, gained special interests as possible prostate chemopreventive agents. Indeed, two large-scale epidemiological studies have demonstrated that finasteride or durasteride significantly reduced the incidence of prostate cancer formation in men. However, these studies have raised an unexpected concern; finasteride and durasteride increased the occurrence of aggressive prostate tumor formation. In the present study, we have observed that treatment of finasteride did not affect the growth of androgen-refractory PC-3 prostate cancer cells. Finasteride also failed to induce apoptosis or affect the expression of proto-oncogenes in PC-3 cells. Interestingly, we found that treatment of finasteride induced the expression of Nrf2 and HO-1 proteins in PC-3 cells. In particular, basal level of Nrf2 protein was higher in androgen-refractory prostate cancer cells, e.g. DU-145 and PC-3 cells, compared with androgen-responsive prostate cancer cells, e.g. LNCaP cells. Also, treatment of finasteride resulted in a selective induction of Nrf2 protein in DU-145 and PC-3 cells, but not in LNCaP cells. In view of the fact that upregulation of Nrf2-mediated phase II cytoprotective enzymes contribute to attenuating tumor promotion in normal cells, but, on the other hand, confers a selective advantage for cancer cells to proliferate and survive against chemical carcinogenesis and other forms of toxicity, we propose that finasteride-mediated induction of Nrf2 protein might be responsible, at least in part, for an increased risk of high-grade prostate tumor formation in men.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.1
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• pp.1-6
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• 2007

Cervical cancer is one of the most prevalent cancers developed in women worldwide, and human papillomavirus(HPV) type 16 is the most common agent linked to human cerivical carcinoma. Viral oncogenes E6 and E7 are selectively retained and expressed in carcinoma cells infected with human papillomavirus type 16 and cooperate with each other in the immortalization and transformation of primary keratinocytes. Because the HPV oncogenesis mechanism was not completely solved, more thorough studies are required. ln the present study, we investigated the telomere independent role of telomerase in HPV oncogenesis, we constructed the E6 mutant, E7, E6/E7 and hTERT over-expressed stable cells with a telomerase negative cell line, SW13. Expressions of inserted genes were measured by RT-PCR. E6, E7 and hTERT genes were well expressed in each cell lines when compared with the control groups. By analyzing the cell morphology under the microscope, hTERT clone size was a smaller than the mock control but oncogene expressed clones had a slightly lengthened marginal region. In addition, hTERT cells also has a tendency of brief dividing time compared to the mock control. To determine whether telomerase activity was associated with a HPV oncogenesis by oncoprotein expression, we performed the PCR based TRAP assay and a Northern blot analysis. In TRAP assay data, telomerase activities in hTERT and oncogene clones increased compared to the mock control. In addition, SW13/E6/E7 cells showed an extremely increased activity compared to the other clones. Induced hTERT mRNA by E6/E7 wasn't, however, detected in Northern blotting. In conclusion, these findings suggest that telomerase activity is closely associated with the HPV oncogenesis and E6/E7 co-expression is a most important factor of telomerase activity.

• The Journal of the Korean Society for Microbiology
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• v.35 no.4
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• pp.299-308
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• 2000

Recently developed cDNA microarray or DNA chip technology allows expression monitoring of expression of hundreds and thousands of genes simultaneously and provides a format for identifying genes as well as changes in their activity. In order to search for changes in gene expression after X irradiation in HL60 cells, cDNA microarray technique was done. In this study, expression of 588 human genes (including oncogenes, tumor suppressor genes, cell cycle regulator genes, intracellular signal transduction modulator genes, apoptosis related genes, transcription factor genes, growth factors and receptor genes, cytokine genes, etc) were analyzed. For cDNA microarray analysis mRNAs were extracted from control and 8 Gy-irradiated HL60 cells. As a result the changes in expression of several genes were observed. This alteration of gene expression was confirmed by reverse transcription-polymerase chain reaction. The expression of heat shock 60 KD protein, c-jun, erythroid differentiation factor, CPP32, myeloid cell nuclear differentiation antigen, MAP kinase-activated protein kinase, interleukin-8, monocyte chemotactic peptide 1 and RANTES genes was increased, but the expression of p55CDC gene was decreased after X irradiation.

• Korean Journal of Head & Neck Oncology
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• v.24 no.2
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• pp.155-161
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• 2008

Head and neck squamous cell carcinoma(HNSCC) still has poor outcome, and laryngeal cancer is the most frequent subtype of HNSCC. Therefore, there is a need to develop novel treatments to improve the outcome of patients with HNSCC. It is critical to gain further understanding on the molecular and chromosomal alteration of HNSCC to identify novel therapeutic targets but genetic etiology of squamous cell carcinoma of the larynx is so complex that target genes have not yet been clearly identified. Array based CGH(array-CGH) allows investigation of general changes in target oncogenes and tumor suppressor genes, which should, in turn, lead to a better understanding of the cancer process. In this study, We used genomic wide array-CGH in tissue specimens to map genomic alterations found in laryngeal squamous cell carcinomas. As results, gains of MAP2, EPHA3, EVI1, LOC389174, NAALADL2, USP47, CTDP1, MASP1, AHRR, and KCNQ5, with losses of SRRM1L, ANKRD19, FLJ39303, ZNF141, DSCAM, GPR27, PROK2, ARPP-21, and B3GAT1 were observed frequently in laryngeal squamous cell carcinoma tissue specimens. These data about the patterns of genomic alterations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information for diagnosis and treatment in laryngeal squamous cell carcinoma. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes which were gained or lost clones.

• Molecules and Cells
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• v.38 no.11
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• pp.925-935
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• 2015

DNA methylation is a well-characterized epigenetic modification that plays central roles in mammalian development, genomic imprinting, X-chromosome inactivation and silencing of retrotransposon elements. Aberrant DNA methylation pattern is a characteristic feature of cancers and associated with abnormal expression of oncogenes, tumor suppressor genes or repair genes. Ten-eleven-translocation (TET) proteins are recently characterized dioxygenases that catalyze progressive oxidation of 5-methylcytosine to produce 5-hydroxymethylcytosine and further oxidized derivatives. These oxidized methylcytosines not only potentiate DNA demethylation but also behave as independent epigenetic modifications per se. The expression or activity of TET proteins and DNA hydroxymethylation are highly dysregulated in a wide range of cancers including hematologic and non-hematologic malignancies, and accumulating evidence points TET proteins as a novel tumor suppressor in cancers. Here we review DNA demethylation-dependent and -independent functions of TET proteins. We also describe diverse TET loss-of-function mutations that are recurrently found in myeloid and lymphoid malignancies and their potential roles in hematopoietic transformation. We discuss consequences of the deficiency of individual Tet genes and potential compensation between different Tet members in mice. Possible mechanisms underlying facilitated oncogenic transformation of TET-deficient hematopoietic cells are also described. Lastly, we address non-mutational mechanisms that lead to suppression or inactivation of TET proteins in cancers. Strategies to restore normal 5mC oxidation status in cancers by targeting TET proteins may provide new avenues to expedite the development of promising anti-cancer agents.

• Preventive Nutrition and Food Science
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• v.8 no.4
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• pp.390-394
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• 2003

In the post-genome period, the technique for identifying gene expression has been progressed to high throughput screening. In the field of molecular nutrition, the use of screening techniques to clarify molecular function of specific nutrients would be very advantageous. In this study, we have evaluated Zn-regulated gene expression in Zn-deficient, homocystein-treated EA.hy926 cells, using cDNA microarray, which can be used to screen the expression of many genes simultaneously. The information obtained can be used for preliminary assessment of molecular and signaling events modulated by Zn under pro-atherogenic conditions. EA.hy926 cells derived from human umbilical vein endothelial cells were cultured in Zn-adequate (control, 15 $\mu$M Zn) or Zn-deficient (experimental, 0 $\mu$M Zn) Dulbecco's MEM media under high homocysteine level (100 $\mu$M) for 3 days of post-confluency. Cells were harvested and RNA was extracted. Total RNA was reverse-transcribed and the synthesized cDNA was labeled with Cy3 or Cy5. Fluorescent labeled cDNA probe was applied to microarray slides for hybridization, and the slide was then scanned using a fluorescence scanner. The expression of seven genes was found to be significantly decreased, and one significantly increased, in response to treatment of EA.hy926 cells with Zn-deficient medium, compared with Zn-supplemented medium. The upregulated genes were oncogenes and tumor suppressor genes, cell cycle-related genes and transporter genes. The down-regulated gene was RelB, a component of the NF-kappaB complex of transcription factors. The results of this study imply the effectiveness of cDNA microarray for expression profiling of a singly nutrient deficiency, namely Zn. Furthur study, using tailored-cDNA array and vascular endothelial cell lines, would be beneficial to clarify the molecular function of Zn in atherosclerosis, more in detail.

• The Journal of the Korean bone and joint tumor society
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• v.3 no.2
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• pp.69-79
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• 1997

Objective : The objective of this study was to compare expression of various proto-oncogenes and rates of apoptosis in osteosarcoma patients. Modulation of apoptosis may influence resistance to chemotherapy and therefore affect the outcome of cancer treatment. Osteosarcoma is one of the most fatal malignancies in young adolescents and investigation of the role of apoptotic cell death is warranted in relation to chemotherapy and tumor outcome. Design : The terminal deoxynucleotidyl transferase to exposed 3'-hydroxyl termini of DNA (TUNEL method) staining method has been applied for the in situ detection of DNA double strand breaks. Patients : Thirty-three osteosarcomas in various stages of differentiation from twenty-nine patients were investigated immunohistochemically for p53, Bcl-2 and TUNEL method for apoptosis. Results and conclusion; We have found that higher level of wild type p53 were correlated with enhanced expression of apoptosis. Increased apoptosis rates were found in cases of negative Bcl-2 expression. In the present study, we have concluded that a significant proportion of osteosarcoma, a tumor in which resistance to chemotherapy often occurs, express high levels of p53 and low levels of Bcl-2. Our data provide further evidence for cross-talk between Bcl-2 and p53 and suggests that these genes are important determinants of drug-induced apoptosis.

• The Korean Journal of Zoology
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• v.33 no.2
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• pp.141-151
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• 1990

Raf protein kinases and protein kinase C belong to serine/threonine-specific proteins in the cytoplasin, and are similar to each other in functional structure and the aspect of the distribution of celI. The distribution of raf protein kinase in the cerebrum of Geoclemys reevesfi as studied by using the antibodies against a-raf and c-raf protein kinase which induce the expression of raf fainily oncogenes. In general, raf protein kinases were distributed in such restricted regions as the general pallium, hippocampal formation, pdmordiuin hippocampi,nucleus of lateral olfactory tract, basal amygdaloid nucleus, and bed of stria terminalis. Immunological labeling of c-raf protein kinase was more widespread than that of a-raf. However, the intensity of the labeling of c-raf was lower than that of a-raf. The spherical cells of basal amygdaloid nucleus is a ring-like form, because only the cytoplasm was imunolabeled. Especially, c-raf protein kinase occurred in the cells which contained protein kinase C abundandy such as pyramidal cells and Purkinje cells. This suggests that a- and e-raf protein kinases may synegistically induce carclnoma with myc gene which is activated by protein kinase C.

• Journal of Microbiology
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• v.45 no.3
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• pp.187-192
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• 2007

REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.