抗癌药物处理后，CD95配体启动子中的一种新型AP-1元件是诱导肝癌细胞凋亡所必需的。
A novel AP-1 element in the CD95 ligand promoter is required for induction of apoptosis in hepatocellular carcinoma cells upon treatment with anticancer drugs.
作者信息
Eichhorst S T, Müller M, Li-Weber M, Schulze-Bergkamen H, Angel P, Krammer P H
机构信息
Tumor Immunology Program, 69120 Heidelberg, Germany.
出版信息
Mol Cell Biol. 2000 Oct;20(20):7826-37. doi: 10.1128/MCB.20.20.7826-7837.2000.
Abstract
The CD95 (also called APO-1 or Fas) system plays a major role in the induction of apoptosis in lymphoid and nonlymphoid tissues in response to a variety of extracellular signals, including chemotherapeutic drugs. Here we report that the CD95 ligand (CD95L) is upregulated in hepatoma cells upon treatment with antineoplastic drugs. Upregulation by different chemotherapeutic drugs is functionally relevant for drug-induced apoptosis and is mediated by transcriptional mechanisms. The MEKK1/JNKK pathway and a novel AP-1 element in the CD95L promoter downstream of the TATA box are required for CD95L upregulation. Thus, understanding the mechanisms of CD95-mediated apoptosis through CD95L upregulation upon treatment of hepatocellular carcinomas with chemotherapeutic drugs may contribute to the improvement of anticancer chemotherapy.
摘要
CD95（也称为APO-1或Fas）系统在响应包括化疗药物在内的多种细胞外信号时，在淋巴组织和非淋巴组织中诱导细胞凋亡过程中发挥主要作用。在此我们报告，用抗肿瘤药物处理后，肝癌细胞中CD95配体（CD95L）上调。不同化疗药物引起的上调在功能上与药物诱导的细胞凋亡相关，且由转录机制介导。TATA框下游的CD95L启动子中的MEKK1/JNKK途径和一个新的AP-1元件是CD95L上调所必需的。因此，了解化疗药物治疗肝细胞癌时通过上调CD95L介导细胞凋亡的机制，可能有助于改善抗癌化疗。
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