Characterization of membrane-associated estrogen receptor signaling pathway in breast cancer cells using selective ligand.

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The existence of membrane-associated ER (mER) in breast dancer cells and relation to hormone therapy resistance has been suggested. However, it is uncertain because of difficulty in distinguishing the signals from nuclear ER (nER) and mER. We developed a selective ligand to mER, Qdot-6-E2. mER is related to cell proliferation in nER positive breast cancer cells via phosphorylation pathway such as ERK and activate nER function. We visually confirmed Qdot-6-E2 diffused in plasma membrane by confocal fluorescence microscopy. nER positive estrogen-depletion resistant cells established from MCF-7 (nER+) treated by Qdot-6-E2 showed dose dependent growth in lower dose than parental cells. These results suggest that ER certainly exists at plasma membrane and makes some contribution to cell growth in nER+ estrogen-depletion resistant cells.