Estrogens are hormones that play central roles in the development and the physiology of the breast, but also are involved in breast cancer. Like all hormones, estrogens exert their biological effects by binding to dedicated receptors in the target cell.
Scientists have now uncovered that half of the luminal epithelial breast cells that appear not to express the estrogen receptor actually express it at low levels. Publishing in Nature Communications, they show that different parts of the estrogen receptor play different roles in the luminal breast cells that give rise to cancer. Depending on whether a cell has low or high levels of the estrogen receptor, the hormone-dependent or the hormone-independent activities are more or less important for its function.
Thirty percent of the luminal cells are ERα-negative by IHC but express Esr1 transcripts. This low level ERα expression through AF-2 is essential for cell expansion during puberty and growth-inhibitory during pregnancy. Cell-intrinsic ERα is not required for cell proliferation nor for secretory differentiation but controls transcript levels of cell motility and cell adhesion genes and a stem cell and epithelial mesenchymal transition (EMT) signature identifying ERα as a key regulator of mammary epithelial cell plasticity.
In addition, the researchers found that the action of the estrogen receptor is biphasic: it stimulates the expansion and growth of breast cells in young mice but inhibits it during pregnancy.
The discovery has immediate implications for the role of ERα in the development of breast cancer. "This begs the question whether these ER-pseudo-negative breast cells will ultimately turn into estrogen receptor-positive or -negative breast cancers," says the author.