Novel Mechanisms by Which Estrogen Induces Antiapoptosis in Breast Cancer

Abstract : We have investigated the interactions between estrogen and caveolin proteins in breast cancer. There is a physical interaction between caveolin-1 and the plasma membrane estrogen receptor in cultured breast cancer cells that is strongly downregulated by estradiol in 30 minutes. This leads to enhanced ERK activation and proliferation of the cells. Overexpressing caveolin-1 leads to a downregulation of the ability of estradiol to activate the ERK (MAP kinase) signal pathway. Estrogen also inhibits caveolin-1 synthesis in breast cancer cells. Caveolin-1 facilitates ER localization to the plasma membrane, demonstrated in breast cancer cells (MCF-7). As for the structure/function of the plasma membrane estrogen receptor, expression and targeting of only the E domain (ligand binding) to the plasma membrane is sufficient for estrogen signaling to ERK. This work was published in Mol Endocrinology 16(1):1OO-115, 2002.