Unlike most organs, mammary glands undergo massive changes during adult life. Epithelial cells proliferate extensively during pregnancy to generate milk for the offspring. When lactation stops, these cells apoptose and the gland is remodelled to its resting state (involution). Baxter and co-workers have been investigating the regulation of involution and, on p. 3485, they report that this process can be halted by the conditional deletion of the gene encoding IKK2 (inhibitor of κB kinase). This is one of the kinases that regulate the nuclear factor-κB (NF-κB) pathway, which controls many cellular responses, including apoptosis. The researchers report that the delayed mammary gland apoptosis and remodelling they see in the conditional mutant is associated with decreased expression of the death receptor ligand TWEAK, which contains binding sites for both NF-κB and FOXO (forkhead transcription factors) in its promoter region. These new insights into the control of apoptosis in a physiological situation may provide new therapeutic approaches to the treatment of breast cancer, suggest the researchers.
TWEAKing mammary gland apoptosis
TWEAKing mammary gland apoptosis. Development 1 September 2006; 133 (17): e1706. doi:
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