Abstract
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.
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Acknowledgements
This work was supported by an AICR grant. AR Clarke is a Royal Society University Research Fellow and CJ Watson is funded by the Cancer Research Campaign.
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Chapman, R., Duff, E., Lourenco, P. et al. A novel role for IRF-1 as a suppressor of apoptosis. Oncogene 19, 6386–6391 (2000). https://doi.org/10.1038/sj.onc.1204016
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DOI: https://doi.org/10.1038/sj.onc.1204016
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