Estrogen receptor-α and progesterone receptor are expressed in label-retaining mammary epithelial cells that divide asymmetrically and retain their template DNA strands

Introduction Stem cells of somatic tissues are hypothesized to protect themselves from mutation and cancer risk through a process of selective segregation of their template DNA strands during asymmetric division. Mouse mammary epithelium contains label-retaining epithelial cells that divide asymmetrically and retain their template DNA. Method Immunohistochemistry was used in murine mammary glands that had been labeled with [H-3] thymidine during allometric growth to investigate the co-expression of DNA label retention and estrogen receptor (ER)-alpha or progesterone receptor ( PR). Using the same methods, we investigated the colocalization of [H-3] thymidine and ER-alpha or PR in mammary tissue from mice that had received treatment with estrogen, progesterone, and prolactin subsequent to a long chase period to identify label-retaining cells. Results Label-retaining epithelial cells (LRECs) comprised approximately 2.0% of the entire mammary epithelium. ER-alpha-positive and PR-positive cells represented about 30 - 40% of the LREC subpopulation. Administration of estrogen, progesterone, and prolactin altered the percentage of LRECs expressing ER alpha. Conclusion The results presented here support the premise that there is a subpopulation of LRECs in the murine mammary gland that is positive for ER-alpha and/or PR. This suggests that certain mammary LRECs ( potentially stem cells) remain stably positive for these receptors, raising the possibility that LRECs comprise a hierarchy of asymmetrically cycling mammary stem/ progenitor cells that are distinguished by the presence or absence of nuclear steroid receptor expression.