Functional Defect of the Fas Mutants Detected in Gastric Cancers
Journal of the Korean Gastric Cancer Association
;
: 186-190, 2003.
Article
in Korean
| WPRIM
| ID: wpr-86902
ABSTRACT
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. MATENRIALS ANDMETHODS:
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Stomach Neoplasms
/
United Nations
/
Transfection
/
Mutagenesis
/
Cell Death
/
Clone Cells
/
Apoptosis
/
DNA, Complementary
/
Fas Receptor
/
Cytoplasm
Type of study:
Prognostic study
Language:
Korean
Journal:
Journal of the Korean Gastric Cancer Association
Year:
2003
Type:
Article
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