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

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. Immunohistochemistry was used in murine mammary glands that had been labeled with [3H]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 co-localization of [3H]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. 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. 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.