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Publication : Functional estrogen receptors in the mitochondria of breast cancer cells.

First Author  Pedram A Year  2006
Journal  Mol Biol Cell Volume  17
Issue  5 Pages  2125-37
PubMed ID  16495339 Mgi Jnum  J:112535
Mgi Id  MGI:3656459 Doi  10.1091/mbc.E05-11-1013
Citation  Pedram A, et al. (2006) Functional estrogen receptors in the mitochondria of breast cancer cells. Mol Biol Cell 17(5):2125-37
abstractText  Steroid hormones have been reported to indirectly impact mitochondrial functions, attributed to nuclear receptor-induced production of proteins that localize in this cytoplasmic organelle. Here we show high-affinity estrogen receptors in the mitochondria of MCF-7 breast cancer cells and endothelial cells, compatible with classical estrogen receptors ERalpha and ERbeta. We report that in MCF-7, estrogen inhibits UV radiation-induced cytochrome C release, the decrease of the mitochondrial membrane potential, and apoptotic cell death. UV stimulated the formation of mitochondrial reactive oxygen species (mROS), and mROS were essential to inducing mitochondrial events of cell death. mROS mediated the UV activation of c-jun N-terminal kinase (JNK), and protein kinase C (PKC) delta, underlying the subsequent translocation of Bax to the mitochondria where oligomerization was promoted. E2 (estradiol) inhibited all these events, directly acting in mitochondria to inhibit mROS by rapidly up-regulating manganese superoxide dismutase activity. We implicate novel functions of ER in the mitochondria of breast cancer that lead to the survival of the tumor cells.
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