The role of ERα36 in cell type-specific functions of estrogen and cancer development

Exploring the regulatory effects of estrogen on different body organs via its receptors is largely of interest. Recently, the expression, signaling and the clinical significance of ER alpha 36, the newly identified isoform of ER alpha, mediating non-genomic signaling of estrogen, have been studied in a wide range of organs and tumors. ER alpha 36 is expressed highly in the CNS and actively involved in neuroprotection. It is also suggested to be an important estrogen receptor involved in preserving bone in postmenopausal women. On the oncological side, although ER alpha 6 has usually been considered to be an oncogenic molecule, results from some studies paradoxically imply its protective role in certain tumors. Collectively, it seems that ER alpha 36 is highly involved in cell type-specific functions of estrogen through its MAPK/ERK signaling, which is dependent on ER alpha 36 expression levels, ligand concentrations and disease stage. The response is also dependent on the levels of E alpha 66 and ER beta. These factors influence the ERK kinetic and determine the ultimate mitogenic or antimitogenic signaling of estrogen, leading to cell survival or cell death. In this review, we summarize the recent organ-specific, cellular and molecular events and the mechanisms involved in estrogen effects mediated through the ER alpha 36/ER alpha 66 with a particular focus on carcinomas where more clinical information has recently emerged.

Automated summary

ER alpha 36, a newly identified isoform of estrogen receptor, is highly expressed in the CNS and plays a role in neuroprotection, as well as maintaining bone density in postmenopausal women. Despite being considered an oncogenic molecule, ER alpha 36 paradoxically may have a protective role in certain tumors according to some studies.