The role of endogenous estrogens in breast cancer etiology has been well-established.However,despite widespread agreement that estrogens are involved in breast cancer etiology,the molecular mechanisms of estrogen action,especially those by which estrogen signaling stimulates mammary tumorigenesis and breast cancer progression have not been well established.Recently,Dr.Wangs group at Creighton University identified and cloned a novel variant of ER-α,which has a molecular weight of 36-kDa and thus termed it ER-α36.ER-α36 is predominantly expressed on the plasma membrane and in the cytoplasm,mediates a membrane-initiated effect of estrogen signaling such as the activation of the MAPK/ERK signaling pathway,and stimulates cell growth (Wang et al.,PNAS 2006).Thus,ER-?36 is a membrane-based estrogen receptor that mediates a membrane-initiated mitogenic estrogen signaling.