Steroid Receptors, Stem Cells and Proliferation in the Human Breast

Abstract

This review summarises the current evidence for adult tissue stem cells in the human breast and examines the role of stemcells, steroids and self-renewal signalling pathways in normal human breast development. The development of the mammary gland is a complex and lengthy process, beginning during embryogenesis and not reaching full functionality until pregnancy and lactation. The gland goes through massive apoptosis and remodelling at the cessation of weaning to resemble once again the non-pregnant gland. The staged and cyclic development of the mammary gland is controlled by ovarian steroids, and it is thought to only be possible due to the presence of adult stem cells. Adult stem cells are self-renewing cells that give rise to all of the functional, differentiated cells of the tissue/organ. The process of self-renewal and stem cell maintenance is tightly controlled and thought to be regulated by signalling, such as through the Notch receptor pathway. Long-livedself-renewing stemcells are thought tobe the targetsof the accumulated mutations that lead to cancer. To fully determine the role of these cells and their signalling in cancer, it is important to first elucidate their function in normal breast development. A great deal of research has now been carried out into the identification and isolation of normal mammary stem cells.