Estrogen receptor alpha-36 (ER-α36): A new player in human breast cancer

Prevailing wisdom is that estrogen receptor (ER)-alpha mediated genomic estrogen signaling is responsible for estrogen-stimulated cell proliferation and development of ER-positive breast cancer. However, accumulating evidence indicates that another estrogen signaling pathway, non-genomic or rapid estrogen signaling, also plays an important role in mitogenic estrogen signaling. Previously, our laboratory cloned a 36 kDa variant of ER-alpha, ER-alpha 36, and found that ER-alpha 36 is mainly expressed in the cytoplasm and at the plasma membrane. ER-alpha 36 mediates rapid estrogen signaling and inhibits genomic estrogen signaling. In this review, we review and update the biological function of ER-alpha 36 in ER-positive and -negative breast cancer, breast cancer stem/progenitor cells and tamoxifen resistance, potential interaction and cross-talk of ER-alpha 36 with other ERs and growth factor receptors, and intracellular pathways of ER-alpha 36-mediated rapid estrogen signaling. The potential function and underlying mechanism of ER-alpha in development of ER-positive breast cancer will also be discussed. (C) 2015 Elsevier Ireland Ltd. All rights reserved.