CELLULAR COMMITMENT TO ONCOGENE-INDUCED TRANSFORMATION OR APOPTOSIS IS DEPENDENT ON THE TRANSCRIPTION FACTOR IRF-1
CELLULAR COMMITMENT TO ONCOGENE-INDUCED TRANSFORMATION OR APOPTOSIS IS DEPENDENT ON THE TRANSCRIPTION FACTOR IRF-1
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DOI：
10.1016/0092-8674(94)90132-5
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发表时间：
1994-06-17
期刊：
影响因子：
64.5
通讯作者：
TANIGUCHI, T
中科院分区：
文献类型：
--
作者：
TANAKA, N;ISHIHARA, M;TANIGUCHI, T
转录激活因子干扰素调节因子1（IRF-1）及其拮抗阻遏因子IRF-2是干扰素（IFN）系统和细胞生长的调节因子。在这里，我们报告说，胚胎成纤维细胞（EFs）与无效突变的IRF-1基因（IRF-1（-/-）小鼠）可以转化的表达激活的c-Ha-ras癌基因。在来自野生型或IRF-2（-/-）小鼠的EF中未观察到该性质，但在来自两种基因缺陷的小鼠的EF中仍观察到该性质。IRF-1cDNA的表达可抑制ras表达IRF-1（-/-）EFs的转化表型。因此，IRF-1起肿瘤抑制剂的作用。此外，c-Ha-ras癌基因的表达导致野生型而不是IRF-1（-/-）EFs进行细胞凋亡时，结合阻断细胞增殖或治疗的抗癌药物或电离辐射。因此，IRF-1可能是癌基因诱导的细胞转化或凋亡的关键决定因素。
The transcriptional activator interferon regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the interferon (IFN) system and of cell growth. Here we report that embryonic fibroblasts (EFs) from mice with a null mutation in the IRF-1 gene (IRF-1(-/-) mice) can be transformed by expression of an activated c-Ha-ras oncogene. This property is not observed in EFs from wild-type or IRF-2(-/-) mice but is still observed in EFs from mice deficient in both genes. The transformed phenotype of ras-expressing IRF-1(-/-) EFs could be suppressed by the expression of the IRF-1 cDNA. Thus, IRF-1 functions as a tumor suppressor. Furthermore, expression of the c-Ha-ras oncogene causes wild-type but not IRF-1(-/-) EFs to undergo apoptosis when combined with a block to cell proliferation or treated by anticancer drugs or ionizing radiation. Hence, IRF-1 may be a critical determinant of oncogene-induced cell transformation or apoptosis.