Prolactin stimulation affects the stem cell-dependent mammary repopulating ability of embryonic mammary anlagen

Abstract

The function of prolactin in mammary gland development and lactation has been demonstrated in previous studies. However, the potential action of prolactin on mammary duct morphogenesis at mammary anlagen stage (E13.5~15.5) has not been elucidated. Transplantation of mammary cells or tissue is an effective approach for the regeneration of damaged mammary gland. Defining the actions of prolactin stimulation on embryonic mammary anlagen has important implications for defining the role of prolactin in the poorly understood processes of mammary duct morphogenesis and regeneration. Here, we have employed the GFP-transgenic mouse model to examine the effects of prolactin on stem cell activity. Using in vitro prolactin stimulation and transplantation of E14.5 mouse mammary anlagen, we identified the influence of prolactin on their mammary repopulating ability. Furthermore, using immunofluorescence staining and microarray analysis, the influence of prolactin on cell characteristics and gene expression in mammary anlagen were also profiled. We also demonstrate that E14.5 mouse mammary anlagen possess mammary stem cells (MaSCs) which achieve mammary repopulation. Furthermore, we found that in vitro prolactin stimulation elevates MaSC activity and promotes the mammary repopulating ability of mammary anlagen. Finally, microarray and pathway analysis showed that MAPK, Akt and JAK-STAT signaling was activated by prolactin stimulation, and drove the mammary repopulation of mammary anlagen. We conclude that prolactin stimulation elevates the stem cell-dependent mammary repopulating ability of embryonic mammary anlagen.