Abstract
BackgroundInhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis. IAPs are frequently dysregulated in cancer, but their role in the regulation of apoptosis during developmental processes is not fully understood. Here we examined the expression of IAPs during the post-natal development of the mouse mammary gland, which is a tissue that exhibits a profound induction of apoptosis during involution.ResultsSix out of eight mammalian IAP family members are expressed in the mammary gland. Notably, quantitative PCR and immunoblotting revealed that XIAP, c-IAP1 and c-IAP2 are down-regulated in pregnancy and lactation, and prior to the onset of involution. In cultured mammary epithelial cells (MECs), XIAP levels decreased in response to inhibition of growth factor signalling. Maintaining XIAP levels in MECs by expressing exogenous XIAP protected them from all apoptotic stimuli tested.ConclusionsThese data suggest that the developmental regulation of IAP expression in vivo contributes to naturally occurring programmes of cell death.
Highlights
Inhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis
BRUCE, c-IAP1, c-IAP2, NAIP1, Survivin and X-linked inhibitor of apoptosis (XIAP) were detected in mouse mammary gland at the time points examined (Figure 1)
These data demonstrate that XIAP is capable of inhibiting apoptosis induced by a variety of stimuli. They suggest that the down-regulation of XIAP contributes to rapid execution of the apoptotic programme. This conclusion is supported by other studies where we have shown that reducing XIAP levels by siRNA does not directly induce apoptosis in mammary epithelial cells (MECs), rather it sensitises cells to apoptosis inducers [18]
Summary
Inhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis. IAPs are frequently dysregulated in cancer, but their role in the regulation of apoptosis during developmental processes is not fully understood. We examined the expression of IAPs during the post-natal development of the mouse mammary gland, which is a tissue that exhibits a profound induction of apoptosis during involution. The mammary gland provides a paradigm to study mechanisms regulating developmental apoptosis [2,3,4,5]. During cycles of mammary gland development, the differentiated epithelial cells that produce milk in lactation undergo widespread apoptosis after weaning, as the gland involutes and remodels to a pre-pregnant state. Elucidating the mechanisms that regulate the sensitivity of mammary epithelial cells (MECs) to apoptosis will provide insight into possible breast cancer targets [6,7].
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