KMID : 0914820030030040186
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Journal of the Korean Gastric Cancer Association 2003 Volume.3 No. 4 p.186 ~ p.190
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Functional Defect of the Fas Mutants Detected in Gastric Cancers
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Park Won-Sang
Cho Yong-Gu Kim Chang-Jae Park Cho-Hyun Kim Young-Sil Kim Su-Young Nam Suk-Woo Lee Sug-Hyung Yoo Nam-Jin Lee Jung-Yong
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Abstract
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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 site- directed 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?3.6%, 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?2.08%, 28.5?3.34%, 25.225?2.06%, and 36.625?4.49%, 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.
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KEYWORD
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Apoptosis, Cell death, Fas, Death receptor, Mutation
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