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

The tumour suppressor IRF-1 is a transcription factor involved in the induc tion of apoptosis in several in vitro systems, Post-lactational involution of the mammary gland is characterized by extensive apoptosis of the epithel ial cells, We have previously shown that signal transducer and activator of transcription (Stat) 3 drives apoptosis and involution in the mouse mammar y 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 o f this transcription factor in involution, Surprisingly, in the absence of IRF-1 significantly higher numbers of apoptotic cells were found in involut ing glands at 48 h compared to control glands, In addition, the alveolar st ructure in IRF-1 null mammary glands had collapsed whereas in control gland s the alveoli remained intact and distended. However, by 72 h control and n ull glands were morphologically similar suggesting that IRF-1 suppresses ap optosis only during the early, reversible, stage of involution, This sugges ts a survival role for IRF-1 in mammary epithelia and demonstrates a novel role for IRF-1 in vivo - suppression of premature epithelial apoptosis duri ng mammary gland involution.