Epigenetic silencing of THY1 tracks the acquisition of the Notch1-EGFR signaling in a xenograft model of CD44+/CD24low/CD90+ myoepithelial cells

The surface glycoprotein Thy1 is a marker of myoepithelial precursor cells, which are basal cells with epithelial-mesenchymal intermediate phenotype originating from the ectoderm. Myoepithelial precursor cells are lost during progression from in situ to invasive carcinoma. To define the functional role of Thy1-positive cells within the myoepithelial population we tracked Thy1 expression in human breast cancer samples, isolated Thy-positive myoepithelial progenitor cells (CD44+/CD24low/CD90+) and established long term cultures (parental cells). Parental cells were used to generate a xenograft model to examine Thy1 expression during tumor formation. Posttransplantation cell cultures loss Thy1 expression through methylation at the THY1 locus and this is associated with an increase in EGFR and Notch1 transcript levels. Thy1-low cells are sensitive to the EGFR/HER2 dual inhibitor lapatinib. High Thy1 expression is associated with poorer relapse-free survival in breast cancer patients. Thy1 methylation may track the shift of bipotent progenitors into differentiated cells. Thy1 is a good candidate biomarker in basal-like breast cancer.