Susceptibility to killer T cells of gastric cancer cells enhanced by mitomycin-C involves induction of ATBF1 and activation of p21 (Waf1/Cip1) promoter
Susceptibility to killer T cells of gastric cancer cells enhanced by mitomycin-C involves induction of ATBF1 and activation of p21 (Waf1/Cip1) promoter
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DOI：
10.1111/j.1348-0421.2004.tb03491.x
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发表时间：
2004-01-01
影响因子：
2.6
通讯作者：
Okada, H
中科院分区：
文献类型：
--
作者：
Miura, Y;Kataoka, H;Okada, H
在胚胎组织中观察到甲胎蛋白（AFP）表达，并且在正常成人组织中不表达该蛋白。血清AFP再次升高，强烈提示成人患有恶性肿瘤。我们在此证明，可以通过低剂量丝裂霉素-C (MMC) 和淋巴因子激活的杀伤 T (LAK-T) 细胞的联合疗法来治疗产生 AFP 的胃癌（AFP-胃癌）。用 MMC 处理 AFP-胃癌细胞可增强其对 LAK-T 细胞的敏感性并诱导 ATBF1 基因表达。我们在此揭示了一种通过 ATBF1 调节 AFP-胃癌细胞细胞周期的新信号通路，该信号通路增强了 p21 (Waf1/Cip1) 基因的启动子活性。免疫沉淀揭示了 ATBF1 和 p53 之间的直接相互作用。与基础活性相比，过表达的 ATBF1 刺激 p21 (Waf1/Cip1) 启动子活性高达 4 倍。 MMC (0.05 mug/ml) 处理后 ATBF1 mRNA 的表达水平加倍。 MMC 处理和 ATBF1 过表达以剂量依赖性方式协同激活 p21 (Waf1/Cip1) 启动子活性，与基础活性相比高达 7 倍。
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 mug/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.