Uncoupling of the ERα regulated morphological phenotype from the cancer stem cell phenotype in human breast cancer cell lines

The CD24low/−CD44+EpCAM+ phenotype is associated with breast cancer initiating cells. To investigate if these putative breast cancer stem cell markers are regulated by estrogen receptor alpha (ERα) we have determined the expression levels of EpCAM, CD44 and CD24 in several well characterized breast cancer cell lines. The expression levels of the three adhesion proteins were quantitatively different in the cell lines but the composite CD24low/−CD44+EpCAM+ breast cancer stem cell phenotype was shown to exist as a small fraction, between 0.1% and 1.2%, in all breast cancer cell lines tested. Experimental silencing of ERα resulted in a reduced epithelial appearance and partial reduction of CD24 mRNA, while levels of CD44 and EpCAM were unaltered. Moreover, knockdown of ERα led to a change in the morphology of the cells similar to the epithelial to mesenchymal transition phenotype and was associated with decreased E-cadherin expression. Our findings offer new insights into the regulation of the breast cancer stem cell phenotype by ERα and suggest that treatments targeting the breast cancer stem cell adhesion molecules and the ERα pathway may be complementary.

Research highlights
► We have analyzed the composite breast cancer stem cell marker phenotype CD24low/-CD44+EpCAM+.
► The composite phenotype exists in a small fraction of cells in breast cancer cell lines.
► Only CD24mRNA level was affected by ERα Knockdown and the effect eas only partial.
► ERα knockdown promoted epithelial to mesenchymal-like transition in cultured cells.
► The morphological effects of ERα knockdown was not associated with an increase of cancer stem cells.