title: A novel role for IRF-1 as a suppressor of apoptosis.
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.
authors.affiliation: Cancer Research Campaign (CRC) Laboratories, Department of Pathology, University of Edinburgh, Medical School, Edinburgh, EH8 9AG, UK.
authors.forename: R S
authors.initials: RS
authors.lastname: Chapman
authors.forename: E K
authors.initials: EK
authors.lastname: Duff
authors.forename: P C
authors.initials: PC
authors.lastname: Lourenco
authors.forename: E
authors.initials: E
authors.lastname: Tonner
authors.forename: D J
authors.initials: DJ
authors.lastname: Flint
authors.forename: A R
authors.initials: AR
authors.lastname: Clarke
authors.forename: C J
authors.initials: CJ
authors.lastname: Watson
mesh_terms: D000818:Animals; D017209:Apoptosis; D001940:Breast / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D050856:Interferon Regulatory Factor-1; D007774:Lactation / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors