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Susceptibility to killer T cells of gastric cancer cells enhanced by Mitomycin-C involves induction of ATBF1 and activation of p21 (Waf1/Cip1) promoter.
- Source :
-
Microbiology and immunology [Microbiol Immunol] 2004; Vol. 48 (2), pp. 137-45. - Publication Year :
- 2004
-
Abstract
- Alpha-fetoprotein (AFP) expression is observed in embryonic tissues and, the expression of this protein is absent in normal adult tissues. The re-elevation of serum AFP strongly suggests generation of a malignant tumor in an adult. We demonstrated here that AFP-producing gastric cancer (AFP-gastric cancer) could be treated by a combination therapy with a low dose of Mitomycin-C (MMC) and lymphokineactivated killer T (LAK-T) cells. Treatment with MMC of AFP-gastric cancer cells enhanced their susceptibility to LAK-T cells and induced ATBF1 gene expression. We revealed here a novel signal pathway for regulation of the cell cycle of AFP-gastric cancer cells through ATBF1, which enhances the promoter activity of the p21 (Waf1/Cip1) gene. Immunoprecipitation revealed the direct interaction between ATBF1 and p53. Overexpressed ATBF1 stimulated p21 (Waf1/Cip1) promoter activity up to 4-fold compared with basal activity. The expression level of ATBF1 mRNA was doubled by MMC (0.05 microg/ml) treatment. The MMC treatment and ATBF1 overexpression synergistically activated the p21 (Waf1/Cip1) promoter activity in a dose-dependent manner up to 7-fold compared with basal activity.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Cyclins physiology
Humans
Repressor Proteins isolation & purification
Signal Transduction
Stomach Neoplasms pathology
Tumor Cells, Cultured
alpha-Fetoproteins physiology
Cyclins metabolism
Gene Expression Regulation, Neoplastic drug effects
Killer Cells, Lymphokine-Activated immunology
Mitomycin pharmacology
Promoter Regions, Genetic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0385-5600
- Volume :
- 48
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Microbiology and immunology
- Publication Type :
- Academic Journal
- Accession number :
- 14978340
- Full Text :
- https://doi.org/10.1111/j.1348-0421.2004.tb03491.x