A novel role for IRF-1 as a suppressor of apoptosis
A novel role for IRF-1 as a suppressor of apoptosis
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DOI：
10.1038/sj.onc.1204016
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发表时间：
2000-12-14
期刊：
影响因子：
8
通讯作者：
Watson, CJ
中科院分区：
文献类型：
--
作者：
Chapman, RS;Duff, EK;Watson, CJ
肿瘤抑制因子IRF-1是一种参与多种体外系统中细胞凋亡诱导的转录因子，乳腺哺乳后退化的特征是上皮细胞的广泛细胞凋亡，我们之前已经证明信号转导子和转录激活子（Stat）3驱动小鼠乳腺的细胞凋亡和退化，由于Stat信号通路的下游靶标之一是IRF-1，我们使用IRF-1敲除小鼠来解决该转录因子在退化中的潜在作用。令人惊讶的是，在不存在IRF-1的情况下，与对照腺体相比，在48小时时在退化腺体中发现了显著更高数量的凋亡细胞。此外，IRF-1无效乳腺中的肺泡结构已经塌陷，而在对照腺体中，肺泡保持完整和膨胀。然而，到72小时，对照和无效腺体在形态上相似，表明IRF-1仅在退化的早期可逆阶段抑制细胞凋亡。这表明IRF-1在乳腺上皮中的存活作用，并证明IRF-1在体内的新作用-在乳腺退化期间抑制过早的上皮细胞凋亡。
The tumour suppressor IRF-1 is a transcription factor involved in the induction of apoptosis in several in vitro systems, Post-lactational involution of the mammary gland is characterized by extensive apoptosis of the epithelial cells, We have previously shown that signal transducer and activator of transcription (Stat) 3 drives apoptosis and involution in the mouse mammary gland, Since one of the downstream targets of the Stat signalling pathway is IRF-1, we have used IRF-1 knockout mice to address the potential role of this transcription factor in involution, Surprisingly, in the absence of IRF-1 significantly higher numbers of apoptotic cells were found in involuting glands at 48 h compared to control glands, In addition, the alveolar structure in IRF-1 null mammary glands had collapsed whereas in control glands the alveoli remained intact and distended. However, by 72 h control and null glands were morphologically similar suggesting that IRF-1 suppresses apoptosis only during the early, reversible, stage of involution, This suggests a survival role for IRF-1 in mammary epithelia and demonstrates a novel role for IRF-1 in vivo - suppression of premature epithelial apoptosis during mammary gland involution.