Estrogen receptors outside the nucleus in breast cancer

Abstract

The estrogen receptor (ER) is the single most powerful predictor of breast cancer prognosis as well as an important contributor to the biology of carcinogenesis. In addition, endocrine therapy targeting ER directly (SERMS) or indirectly (aromatase inhibitors) forms the mainstay of adjuant therapy. Traditionally, human tumors are scored for the amount and presence of ER. However, this has centered on the population of ER found in the transformed epithelial cell nucleus. Over the last 40 years, it has been appreciated that additional cellular ER pools exist, in cytoplasm and at the plasma membrane. In this review, we discuss the important functions of extra-nuclear ER in breast cancer, including integration of function with nuclear ER.

Non-nuclear estrogen receptor α signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice

“…Our in vivo findings for the tumors are entirely consistent with the growth that occurs with E 2 but not with EDC treatment of MCF-7 cells in culture (11). Thus, although there is considerable in vitro evidence that signaling by non-nuclear ER positively influences the properties of breast cancer cells through diverse mechanisms including the modification of gene expression (11,41,42), non-nuclear ER signaling alone is not sufficient to stimulate the growth of breast cancer cells in culture or in vivo.…”

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

“…Alternatively, ER interacts with other transcription factors, indirectly modulating gene expression (Marino et al, 2006). In addition to the nuclear action of ER, plasma membrane and cytoplasmlocalized ER activate multiple signaling pathways and exert rapid effects upon estrogen stimulation (Kampa et al, 2008;Levin and Pietras, 2008).…”

A bi-faceted role of estrogen receptor β in breast cancer

“…Rapid, non-genomic activities of estrogen are thought to be mediated by ERs localized to the plasma membrane on some target cells (Levin & Pietras 2008). With respect to differential subcellular localization of ERb-like proteins, extranuclear vs nuclear localization has been reported to provide differential prognostic information at least in breast cancer in vivo (Shaaban et al 2008.…”