Membrane-initiated estrogen signaling: oncogenic or impotent?

A recent study by Kampa et al. provided further evidence of nongenomic, membrane-initiated estrogen signaling. Using a cell-impermeable estradiol-bovine serum albumin conjugate, the authors identified genes and kinases that were modulated by a membrane-associated estrogen receptor, which they have termed 'ERx.' They describe how estradiol-induced ERx function is insensitive to antiestrogens tamoxifen and fulvestrant. The ERx components upregulated kinase signaling pathways and genes implicated in cancer progression, suggesting that ERx may promote antiestrogen resistance. However, the existence of membrane-initiated estrogen signaling and its contribution to antiestrogen resistance in vivo await confirmation.