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Mechanisms of Hormone Carcinogenesis:

Evolution of Views, Role of Mitochondria

  • Chapter
Innovative Endocrinology of Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 630))

Abstract

Cumulative and excessive exposure to estrogens is associated with increased breast cancer risk. The traditional mechanism explaining this association is that estrogens affect the rate of cell division and apoptosis and thus manifest their effect on the risk of breast cancer by affecting the growth of breast epithelial tissues. Highly proliferative cells are susceptible to genetic errors during DNA replication. The action of estrogen metabolites offers a complementary genotoxic pathway mediated by the generation of reactive estrogen quinone metabolites that can form adducts with DNA and generate reactive oxygen species through redox cycling. In this chapter, we discussed a novel mitochondrial pathway mediated by estrogens and their cognate estrogen receptors (ERs) and its potential implications in estrogen-dependent carcinogenesis. Several lines of evidence are presented to show: (1) mitochondrial localization of ERs in human breast cancer cells and other cell types; (2) a functional role for the mitochondrial ERs in regulation of the mitochondrial respiratory chain (MRC) proteins and (3) potential implications of the mitochondrial ER-mediated pathway in stimulation of cell proliferation, inhibition of apoptosis and oxidative damage to mitochondrial DNA. The possible involvement of estrogens and ERs in deregulation of mitochondrial bioenergetics, an important hallmark of cancer cells, is also described. An evolutionary view is presented to suggest that persistent stimulation by estrogens through ER signaling pathways of MRC proteins and energy metabolic pathways leads to the alterations in mitochondrial bioenergetics and contributes to the development of estrogen-related cancers.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, 22908-0546, USA

    Jin-Qiang Chen

  2. Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

    Terry R. Brown

  3. Department of Environmental Health Sciences, Johns Hopkins Bloomberg Schoolof Public Health, Baltimore, Maryland, USA

    James D. Yager

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  1. Jin-Qiang Chen
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  2. Terry R. Brown
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  3. James D. Yager
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Correspondence to Jin-Qiang Chen .

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Editors and Affiliations

  1. Laboratory of Oncoendocrinology, Professor N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia

    Lev M. Berstein MD, PhD, DMS

  2. Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    Richard J. Santen MD

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Chen, JQ., Brown, T.R., Yager, J.D. (2008). Mechanisms of Hormone Carcinogenesis:. In: Berstein, L.M., Santen, R.J. (eds) Innovative Endocrinology of Cancer. Advances in Experimental Medicine and Biology, vol 630. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78818-0_1

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