A novel role for IRF-1 as a suppressor of apoptosis

Chapman, Rachel S., Duff, Eleanor K., Lourenco, Paula C., Tonner, Elizabeth, Flint, David J., Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X and Watson, Christine J. 2000. A novel role for IRF-1 as a suppressor of apoptosis. Oncogene 19 (54) , pp. 6386-6391. 10.1038/sj.onc.1204016

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	Q Science > Q Science (General) Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords:	IRF-1; apoptosis; mammary gland; involution.
Publisher:	Nature Publishing
ISSN:	0950-9232
Last Modified:	25 Oct 2022 10:11
URI:	https://orca.cardiff.ac.uk/id/eprint/61379

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