The role of estradiol and the estrogen receptor (ER-α) in the etiology of breast cancer have long been appreciated. This understanding has been complicated by two discoveries in the 1990s: (1) a second estrogen receptor (ER-β) whose expression pattern and activity overlap with but are distinct from those of ER-α; and (2) a pool of ERs located at the plasma membrane. This plasma membrane-localized ER constitutes a distinct pool of receptors whose protein interactions, signaling mechanisms, and cellular functions are not the same as that of the cytoplasmic- and nuclear-localized ER and are not as well understood. Here, we will consider the structure and function of the membrane-localized ER protein. We will then discuss what is known about the role of the membrane ER in the development and its implications for breast cancer treatment.
