http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Hypermethylation of the RUNX3 gene in hepatocellular carcinoma
박원상,조영구,김창재,송재휘,이연수,김수영,남석우,이석형,유남진,이종영 생화학분자생물학회 2005 Experimental and molecular medicine Vol.37 No.4
Methylation events play a critical role in various cellular processes including regulation of gene transcription and proliferation. Recently, RUNX3 β-Smads signaling transduction pathway genes, showed strong tumor-suppressor activity by regulation of epithelial proliferation and apoptosis. To elucidate the potential etiological role of the RUNX3 gene in the development of hepato-cellular carcinoma (HCC), we have analyzed the methylation status of 5' CpG island of the RUNX3 gene in a series of 73 HCC tissues and 1 liver cell lines. Expectedly, promoter methylation of RUNX3 gene was found in 2 (2.7%) of 73 corresponding normal liver, whereas 30 (41.1%) of 73 HCCs and 4 (40%) of 10 liver cancer cell lines showed hypermethylation of the gene, respectively. There was no significant difference between promoter hypermethylaion and clinicopathologic parameters of primary HCC sam-ples, including histologic grade, microvascular invasion, and clinical stage. Interestingly, demethy-lating agent 5-aza-2-deoxycytidine induced reacti-vation and more potent expression of RUNX3 gene in HCC cell lines. Our findings indicate that promoter hypermethylation of RUNX3 gene may occur as an early event in the development of HCC and that methylation may be a major mechanism for inactivation of RUNX3 gene in HCC.
박원상,조장,이화성,송재휘,윤정환,박용규,남석우,이정용 대한병리학회 2010 Journal of Pathology and Translational Medicine Vol.44 No.4
Background : Osteoarthritis (OA) is a common disease characterized by degenerating joint cartilage in the knee, hip, and hand. A functional single nucleotide polymorphism (SNP) +104-T/C; rs143383 in the 5′untranslated region of the growth differentiation factor 5 (GDF5) gene was recently associated with susceptibility to OA in the Japanese and Chinese populations. Methods : To investigate whether this association is present in the Korean population, the frequency of the polymorphism was investigated in 276 patients with knee OA and 298 healthy subjects as controls. Polymorphism analysis was performed by amplifying the core promoter region of the GDF5 gene and digesting it with the BsiEI restriction enzyme. Results : The frequency of the TT, CT, and CC genotypes was 54.3% (150/276), 41.7% (115/276), and 4.0% (11/276), respectively, in patients with OA, and 53.4% (159/298), 37.9% (113/298), and 8.7% (26/298), respectively, in healthy controls. No significant differences in genotypic or allelic frequencies of the +104T/C SNP of the GDF5 gene were observed between patients with OA and controls. Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by age and gender. Conclusions : The results suggest that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA in the Korean population.
위 선종 및 선암에서 Trefoil Factor Family 1 단백의 발현 양상
박원상,김영실,유남진,박조현,유진영,이연수,이정용,Park Won Sang,Kim Young Sil,Yoo Nam Jin,Park Cho Hyun,Yoo Jin Young,Lee Youn Soo,Lee Jung Young 대한위암학회 2001 대한위암학회지 Vol.1 No.1
Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.
박원상,조용구,김창재,박조현,김영실,김수영,남석우,이석형,유남진,이정용,Park Won Sang,Cho Young Gu,Kim Chang Jae,Park Cho Hyun,Kim Young Sil,Kim Su Young,Nam Suk Woo,Lee Sug Hyung,Yoo Nam Jin,Lee Jung Young 대한위암학회 2003 대한위암학회지 Vol.3 No.4
Purpose: The balance between cell proliferation and apoptosis is crucial for homeostatic maintenance in a cell population. Decreased apoptosis or uncontrolled proliferation can lead to cancer. The Fas receptor signal through a cytoplasmic death domain is very important in the apoptotic pathway. To identify the effect of the death domain of the Fas gene in the development and/or progression of gastric cancer, we examined the apoptotic potential of five known Fas mutants detected in gastric cancers. Materials and Methods: A wild-type Fas gene was cloned with cDNA from normal liver tissue and full length Fas was sequenced. Mutants of the gene were generated with sitedirected mutagenesis by using the wild-type gene and specific primers. Wild- and mutant-type genes were transfected to HEK293 cells. Forty-eight hours after transfection the cells were stained with DAPI and cell death was counted under fluorescent microscopy. Results: In wild-type Fas-transfected cells, the percentage of apoptotic cells was $85.9\pm3.6\%$, and significant cell death and classic morphologic signs of apoptosis were observed. However, the percentages of apoptotic cells transfected with N239D, E240G, D244V, and R263H of tumor-derived mutant Fas were $29.5\pm2.08\%,\;28.5\pm3.34\%,\;25.225\pm2.06\%,\;and\;36.625\pm4.49\%$, respectively. Conclusion: These results suggest that inactivation of Fas caused by mutations in the death domain of the Fas gene may be one of the possible escape mechanisms against Fas-mediated apoptosis and that inactivating mutation of the Fas may contribute to the development or progression of gastric cancers.
Molecular Pathogenesis of Gastric Cancer
박원상 대한의사협회 2010 대한의사협회지 Vol.53 No.4
In this article, I will survey the major genetic susceptibility and somatic genetic alterations involved in gastric cancer and adenoma. These include germline and somatic genetic alterations in oncogenes, tumor suppressor genes, and apoptosis-related genes. A small proportion of gastric cancers arise as a consequence of hereditary predisposition caused by specific germline mutations in E-cadherin, mismatch repair genes, adenomatous polyposis coli,and STK11. Aberrant expression of activation induced cytidine deaminase, triggered by Helicobacter pylori infection, accumulates with genetic mutations of oncogenes and tumor suppressor genes, including p53 and CTNNB1. Inactivation of trefoil factor family 1, which is a gastric specific tumor suppressor, occurs in gastric adenomas and cancers. Ectopic expression of CDX2 leads to intestinal metaplasia and defective Cdx2 expression accelerates the transformation of metaplastic cells to gastric cancer. Genetic alterations of p53 and genes related to Wnt signaling pathway and microsatellite instability occur early in the development of gastric carcinoma, indicating that detection of certain genetic alterations in adenomas may be indicative of malignant transformation. In addition, inactivation of apoptosis-inducing gene caused by mutations may be an escaping mechanism against apoptotic cell death and contribute to the progression of gastric cancer. Although the results of many studies are contradictory with one another, genetic alterations in oncogenes and tumor suppressor genes are present even in gastric adenoma and increase in frequency during multistep gastric carcinogenesis. Genetic alterations described herein, and from as yet unidentified target genes in gastric cancer cells, will guide us towards more effective risk assessment, diagnosis, and treatment.