[...]... targeted to mammary epithelial SCs The first evidence to support the notion of mammary SCs came from murine transplantation experiments Mammary gland tissue was removed from a donor mouse and transplanted into the cleared mammary fat pad of a recipient mouse, regenerating a fully functional mammary gland (Deome et al 1959) More recently, transplantation of mammary epithelia marked with mouse mammary. .. inhibitory factor is able to modulate the Wnt/β- Progesterone and Wnt Signalling 13 Fig 2a, b The Wnt/β-catenin signalling pathway a In mammary epithelium, progesterone (Pg) binds to its receptor (PR) within the cell nucleus Wnt proteins are in turn expressed, activated and secreted from the cell These secreted extracellular Wnt proteins are then able to bind to the transmembrane receptor Frizzled and. .. cells from this subpopulation had the ability to produce the normal heterogeneous structure of the gland, suggesting that these cell markers are not sufficient to completely mark the SC (Shackleton et al 2006) The subpopulation can be further enriched using a CD49f+ sort with 1 in 20 R Lamb, H Harrison, R.B Clarke 8 mouse mammary cells from this population having the ability to regenerate the entire gland. .. that the dye Hoechst 33342 is toxic to cells; perhaps cells that can efflux the dye are able to form mammary glands and mammospheres simply because they are left unharmed when compared to the cells which are unable to efflux the dye This method, therefore, may not be the most suitable for the identification of mammary SCs (Smalley and Clarke 2005) 7 Cell Surface Markers A more appropriate method may be the. .. through the Wnt pathway to increase SC self-renewal 2 Mammary Gland Development Mammary gland development begins during embryogenesis, with the formation of a rudimentary ductal system and remains virtually unaltered throughout childhood (Naccarato et al 2000) During puberty, hormonal changes induce the formation of networks of epithelial ducts which grow outwards from the nipple and divide into primary and. .. receptors and low-density lipoprotein receptor protein 5/6 (LRP5/6) (Bejsovec 2005; Bhanot et al 1996) Binding of Wnt to Frizzled receptor results in the phosphorylation of the cytoplasmic mediator Dishevelled, and the inhibition of the multifunctional serine/ threonine kinase GSK3β (Doble and Woodgett 2003) When GSK3β is inactive, β-catenin accumulates within the cytoplasm and translocates to the nucleus... observed with the use of exogenous ovarian hormones in the form of the oral contraceptive pill or hormone replacement therapy (Clemmons and Gross 2001; Travis and Key 2003) Ovarian hormones have been shown to exert their effects through ligand-activated steroid receptors in the mammary epithelium Approximately 10%–15% of the cells within the epithelium coexpress oestrogen receptor alpha (ERα) and progesterone... be detected from the early stages of embryonic mammary development and continues into puberty (Lane and Leder 1997) Wnt signalling plays a significant role in normal mammary gland development when expression begins at embryonic day 10.5 with the formation of two mammary lines” (Veltmaat et al 2003) In response to signals from the underlying mesenchyme, the mammary lines give rise to five mammary placodes... within the breast, at least partly, by regulating the mammary stem cell population 1 Introduction This review aims to discuss the role of progesterone and its downstream targets such as Wnt in mammary gland development and breast carcinomas Evidence is accumulating to suggest that stem cells (SCs) are involved in both normal mammary gland development and the formation of breast carcinomas We hypothesise... ductal side branching and the alveolar development of the mammary gland whereas chimeric epithelia of PR–/– cells and wild-type cells undergo complete alveolar development, suggesting a secreted local factor (Brisken et al 1998) Together these data suggest that the proliferation of ERα/PR-negative cells is controlled by a paracrine mediator of the systemic hormonal signal and fits with the finding that proliferating . 2007-1 Progestins and the Mammary Gland Ernst Schering Foundation Symposium Proceedings 2007-1 Progestins and the Mammary Gland From Basic Science to Clinical. development, the Ernst Schering Foundation held a symposium on Progestins and the Mammary Gland From Ba- sic Science to Clinical Applications . The present