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B) Estradiol-induced protein complex formation among ER_ , SHC and IGF-1-R. 1 nM for the times indicated. Lysates were immunoprecipitated with IGF-1-R antibody. 28 C) Estradiol increases the phosphorylation of the IGF-1-R. Adaptation to Estradiol Deprivation Causes Up-Regulation of Growth Factor Pathways 27 E2 treatment. 20 The pure estrogen receptor antagonist, fulvestrant, blocked E2-induced SHC and MAPK phosphorylation at 3 min and 15 min respectively. To demonstrate that the classical ER alpha mediated this response, we transfected a siRNA against ER alpha and showed down-regulation of this receptor and also abrogated the effect of estradiol to rapidly enhance MAP kinase activation.
Levin ER. Integration of the extranuclear and nuclear actions of estrogen. Mol Endocrinol 2005; 19(8):1951-59. 9. Chen JQ, Eshete M, Alworth WL et al. Binding of MCF-7 cell mitochondrial proteins and recombinant human estrogen receptors alpha and beta to human mitochondrial DNA estrogen response elements. J Cell Biochem 2004; 93(2):358-73. 10. Chen JQ, Yager JD. Estrogen’s effects on mitochondrial gene expression: mechanisms and potential contributions to estrogen carcinogenesis. Ann N Y Acad Sci 2004; 1028258-72.
Mechanisms of the deleterious effects of tamoxifen on mitochondrial respiration rate and phosphorylation efficiency. Toxicol Appl Pharmacol 2001; 176(3):145-52. 138. Cardoso CM, Moreno AJ, Almeida LM et al. 4-Hydroxytamoxifen induces slight uncoupling of mitochondrial oxidative phosphorylation system in relation to the deleterious effects of tamoxifen. Toxicology 2002; 179(3):221-32. 139. Cardoso CM, Moreno AJ, Almeida LM et al. Comparison of the changes in adenine nucleotides of rat liver mitochondria induced by tamoxifen and 4-hydroxytamoxifen.