Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland

作者：Mona Shehata, Andrew E. Teschendorff, Gemma Sharp, Nikola Novcic, I. Alasdair Russell, Stefanie Avril, Michael Prater, Peter Eirew, Carlos Caldas, Christine J. Watson, Julia Stingl · 发表于：Breast Cancer Research · 年份：2012 · DOI：10.1186/bcr3334 · 被引用次数：308 · 研究领域：Cancer Cells and Metastasis、Estrogen and related hormone effects、Breast Cancer Treatment Studies

INTRODUCTION: The organisation of the mammary epithelial hierarchy is poorly understood. Our hypothesis is that the luminal cell compartment is more complex than initially described, and that an understanding of the developmental relationships within this lineage will help in understanding the cellular context in which breast tumours occur. METHODS: We used fluorescence-activated cell sorting along with in vitro and in vivo functional assays to examine the growth and differentiation properties of distinct subsets of human and mouse mammary epithelial cells. We also examined how loss of steroid hormones influenced these populations in vivo. Gene expression profiles were also obtained for all the purified cell populations and correlated to those obtained from breast tumours. RESULTS: The luminal cell compartment of the mouse mammary gland can be resolved into nonclonogenic oestrogen receptor-positive (ER+) luminal cells, ER+ luminal progenitors and oestrogen receptor-negative (ER-) luminal progenitors. The ER+ luminal progenitors are unique in regard to cell survival, as they are relatively insensitive to loss of oestrogen and progesterone when compared with the other types of mammary epithelial cells. Analysis of normal human breast tissue reveals a similar hierarchical organisation composed of nonclonogenic luminal cells, and relatively differentiated (EpCAM+CD49f+ALDH-) and undifferentiated (EpCAM+CD49f+ALDH+) luminal progenitors. In addition, approximately one-quarter of hu...