Mammary gland involution as a multi-step process.

Mammary gland involution is a highly complex multi-step process in which the lactating gland returns to a morphologically near pre-pregnant state. This developmental stage is characterized by a high degree of epithelial cell death, redevelopment of the mammary adipose tissue and tissue remodelling. Many factors involved have been described and these have been reviewed intensively in this journal (Furth, P. A., J. Mammary Gland Biol. Neoplasia, 4:123-127, 1999) and elsewhere. Microarray analysis technology has now not only allowed us to identify genes not previously associated with involution (Stein, T., Morris, J.S., Davis, C.R.,Weber-Hall, S.J., Duffy, M.A., Heath, V.J., et al., Breast Cancer Res., 6: R75-R91, 2004; Clarkson, R.W., Wayland, M.T., Lee, J., Freeman, T., Watson, C.J., Breast Cancer Res., 6: R92-R109, 2004; Clarkson, R.W., Watson, C.J., J. Mammary Gland Biol. Neoplasia, 8: 309-319, 2003), it has also enabled us to define multiple phases of the controlled regulatory response to forced weaning on the basis of their transcriptional profiles. This review provides a synthesis of published data, integrating the time course of transcriptional activity in the mouse mammary gland with a gene ontology approach to identify the pathways involved.