Breastmilk and the lactating breast as a tool to elucidate breast cancer

Abstract

Mammary stem cells (MaSCs) are responsible for the normal expansion of the breast during pregnancy/lactation. MaSCs are also primary targets of malignant transformation, giving rise to invasive breast carcinomas, a subset of which display lactating features. We have recently reported expression of OCT4 and associated embryonic stem cell (ESC) genes in the normal lactating breast and breastmilk stem cells (hBSCs). This prompted us to examine OCT4 expression in breast cancers with lactating features and to compare it with that observed during normal lactation. Minimal OCT4 expression was found in the normal resting breast, whereas this significantly increased in the normal lactating breast. Further increase was found in breast tumours with lactating features. Comparison of normal hBSCs with OCT4‐overexpressing tumorigenic breast cell lines (OTBCs) showed that OTBCs had unbalanced expression of ESC genes. Similar to hBSCs, OTBCs differentiated into functional lactocytes synthesising milk proteins both in vitro and in vivo. These findings highlight ESC genes as potential regulators of the normal remodelling of the breast towards a milk‐secretory organ and of aberrant breast cell proliferation upon deregulation of their expression, suggesting a role in both normal lactation and breast oncogenesis.Grant Funding Source: Women and Infants Research Foundation; and Medela AG (Switzerland)