Colony-forming assays that use mammary stem-like cells (M...

Colony-forming assays that use mammary stem-like cells (MaSC)/bipotent progenitor cells isolated from normal adult human mammary glands, show that MaSC form mixed colonies which include luminal progenitor cells (Stingl et al. 2005, Raouf et al. 2008, Hilton et al. 2012). For a detailed description of MaSCs/bipotent mammary gland progenitors, please refer to the module Developmental Lineage of Mammary Stem Cells. A small number of basally-located bipotent progenitors/MaSCs in normal adult human mammary glands express progesterone receptor (PGR) (Hilton et al. 2012, Tharmapalan et al. 2025). It has been hypothesized that these PGR+ MaSCs respond to circulating progesterone to expand the luminal progenitor compartment during the luteal phase of the menstrual cycle and during preparation for lactation in pregnancy (Hilton et al. 2012). However, a subsequent study reported that MaSCs express PGR at the mRNA but not protein level (Nguyen et al. 2018). A mouse lineage tracing study showed that PGR+ subpopulation of basally located bipotent progenitors, just like the PGR- subpopulation, gives rise to both mature myoepithelial and mature luminal cells (Tharmapalan et al. 2025), but an earlier study reported that only ESR- luminal progenitors in mouse share the ancestry with myoepithelial progenitors (Wang et al. 2017). In ESR+ luminal progenitors, however, PGR expression is very low, but ESR+ luminal progenitors give rise to mature luminal cells that are also PGR+ (Hilton et al. 2012). Lineage tracing studies in mouse show that luminal progenitor cells that are positive for the cell surface marker PROM1 (also known as CD133) are also ESR+ and negative for the transcription factor SOX9 (Wang et al. 2017). These PROM1+ESR+ luminal progenitors give rise exclusively to ESR-positive mature luminal cells (Wang et al. 2017). ESR-positive luminal progenitors might be derived from the SOX9- subpopulation of MaSCs (Wang et al. 2017). A mouse study showed that the cell surface glycoprotein MCAM (also known as MUC18 or CD146) maintains the ESR-positive luminal progenitor state, which is dependent on MCAM-mediated inhibition of CK2 and STAT3 signaling (Balcioglu et al. 2024). In contrast, in human mammary gland MCAM is expressed at a low level in hormone receptor positive mature luminal cells, is expressed at a high level in hormone receptor negative luminal progenitor cells, but is not specific for the luminal compartment (Isberg et al. 2019).

Markers or hormone receptor positive luminal progenitors are listed in the table below (in the table, "No" means that the marker is not listed for the specified cell type while "N/A" means that the specified cell type is not annoted in the cited external marker database).

EGFR protein is detectable at the surface of ~ 50% of luminal progenitor cells derived from MaSC-like cells of the normal adult human breast (Stingl et al. 2001). EGFR is detectable in luminal progenitor cells derived from MCF10A human mammary epithelial cell line but expressed at a lower level than in MaSCs and myoepithelial progenitor cells (Phillips et al. 2014). EGFR is therefore not annotated as a marker of human mammary luminal progenitor cells.

EGFR ligands EGF and AREG stimulate in vitro differentiation of MaSCs into luminal lineage, while EGFR ligand TGFA inhibits it (Pasic et al. 2011, Mukhopadhyay et al. 2013).

Expression of NOTCH4 mRNA, which is associated with MaSC phenotype (Bachelard-Cascales et al. 2010, Lim et al. 2010, Coradini et al. 2014), is downregulated in mammary luminal progenitor cells (Coradini et al. 2014).

KRT18 mRNA expression in mammary luminal progenitor cells of normal adult human breast is low compared to mature luminal epithelial cells (Prat et al. 2013). KRT8 is expressed at a low level in luminal progenitor cells and thus not annotated as a marker (Nguyen et al. 2018).