Faculty Publications

Chen J, Russo J

Mitochondrial oestrogen receptors and their potential implications in oestrogen carcinogenesis in human breast cancer

J Nutr Environ Med. 2008;17(1):76-89.

Abstract Background. Prolonged exposure to estrogens (17b-estradiol)(E2), xenoestrogens, hormone replacement therapy and contraceptives has been recognized as a key etiological factor of human breast cancer. The biol. and carcinogenic effects of E2 and xenoestrogens are mediated via estrogen receptors alpha (ERa) and beta (ERb). Both receptors are localized in the nucleus of E2-targeted cells including human breast cells where they are involved in the regulation of nuclear gene expression. There is increasing evidence indicating that a small fraction of total cellular ERs, particularly ERa, are localized in the membrane of E2-targeted cells where they mediate E2-dependent and/or E2-independent rapid and non-nuclear genomic signal pathways. Results. The present work will present evidence that: (1) there is mitochondrial localization of ERs in human breast cancer cells; (2) there is a functional role of the mitochondrial ERs in the regulation of mitochondrial genes encoding respiratory chain proteins. Conclusions. The potential implications of the mitochondrial ER-mediated pathways in estrogen carcinogenesis, particularly in stimulation of cell proliferation and inhibition of apoptosis, in human breast cancer and the potential nutritional and environmental perspectives of these effects will be addressed. [on SciFinder (R)]