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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
Author(s) -
Miura Yutaka,
Kataoka Hiromi,
Joh Takashi,
Tada Toyohiro,
Asai Kiyofumi,
Nakanishi Makoto,
Okada Noriko,
Okada Hidechika
Publication year - 2004
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2004.tb03491.x
Subject(s) - mitomycin c , biology , cancer research , cancer , cancer cell , basal (medicine) , microbiology and biotechnology , endocrinology , genetics , insulin
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 lymphokine‐activated 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 μg/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.