Breast Stem Cells and Cancer

Breast Biology Group, School of Cancer and Imaging Sciences, Faculty of Medicine and Human Sciences, University of Manchester, Paterson Institute for Cancer Research, Wilmslow Road, M20 4BX Manchester, UK email:[email protected]

3 DCIS Mammospheres—Importance of EGF and Notch Signalling 147

Abstract. Recent results have increased our understanding of normal stem cells and the signalling pathways which regulate them during the development of the mammary gland. Tumours in many tissues are now thought to develop from dysregulated stem cells and depend on activated stem cell self-renewal pathways such as Notch for their tumourigenic capacity. These cancer stem cells are recognised by specific cell surface proteins that they express and their capacity to grow tumours in vivo or spheres in vitro. We have described human breast DCIS mammospheres grown from cancer stem cells and demonstrated their dependence on the EGF and Notch receptor pathways. Stem cell self-renewal pathways such as these may represent novel therapeutic targets to prevent recurrence of pre-invasive and invasive breast cancer.

1 Introduction

Adult stem cells are defined by their capacity for self-renewal and differentiation into cell lineages present in a specific tissue (Morrison et al. 1997; Weissman 2000). The adult mammary gland has a lobulo-alveolar structure, composed of three cell lineages: myoepithelial cells which form the basal layer of ducts and alveoli; ductal epithelial cells which line the lumen of ducts and alveolar epithelial cells which synthesise

2 Cancer Stem Cells

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