Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the expression of Fas
Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the expression of Fas
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DOI：
10.1093/emboj/18.7.1824
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发表时间：
1999-04-01
期刊：
影响因子：
11.4
通讯作者：
Tschopp, J
中科院分区：
文献类型：
--
作者：
Peli, J;Schröter, M;Tschopp, J
肿瘤生长是组织稳态失控的结果，组织稳态是通过细胞生长和细胞凋亡的微妙平衡来维持的，细胞凋亡最有效的诱导剂之一是死亡受体Fas，我们在此报道致癌Ras (H-Ras)下调Fas表达并使成纤维细胞和上皮样来源的细胞对Fas配体诱导的细胞凋亡产生抵抗，在Ras转化的细胞中，Fas mRNA不存在。 DNA 甲基化的抑制可恢复 Pas 表达。 H-Ras 通过 PI 3 激酶途径发出信号来下调 Fas，这表明下游 PKB/Akt 激酶的已知抗凋亡作用可能至少部分是通过抑制 Fas 表达来介导的。因此，H-ras 的致癌潜力可能不仅在于其促进细胞增殖的能力，而且还在于其同时抑制 Fas 触发的细胞凋亡的能力。
Tumor growth is the result of deregulated tissue homeostasis which is maintained through the delicate balance of cell growth and apoptosis, One of the most efficient inducers of apoptosis is the death receptor Fas, We report here that oncogenic Ras (H-Ras) downregulates Fas expression and renders cells of fibroblastic and epitheloid origin resistant to Fas ligand-induced apoptosis, In Ras-transformed cells, Fas mRNA is absent. Inhibition of DNA methylation restores Pas expression. H-Ras signals via the PI 3-kinase pathway to downregulate Fas, suggesting that the known anti-apoptotic effect of the downstream PKB/Akt kinase may be mediated, at least in part, by the repression of Fas expression. Thus, the oncogenic potential of H-ras may reside on its capacity not only to promote cellular proliferation, but also to simultaneously inhibit Fas-triggered apoptosis.