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Catechol Estrogen 4-Hydroxyestradiol is an Ultimate Carcinogen in Breast Cancer
Biomed. Sci. Lett. 2018;24:143-149
Published online September 30, 2018;  https://doi.org/10.15616/BSL.2018.24.3.143
© 2018 The Korean Society For Biomedical Laboratory Sciences.

Sin-Aye Park,*

Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan 31538, Korea
Correspondence to: Sin-Aye Park. Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan 31538, Korea.
Tel: +82-41-530-4990, Fax: +82-41-530-3085, e-mail: sappark@sch.ac.kr
*Professor.
Received June 7, 2018; Revised September 1, 2018; Accepted September 4, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Excessive exposure to estrogens is the most important risk factor for the development of hormone-sensitive cancers, especially breast cancer. Estrogen stimulates the expression of genes and proteins involved in cell proliferation by binding to estrogen receptor (ER). Another possible mechanism of ER-independent carcinogenicity of estrogens is based on the hydroxylation of estradiol resulting in the formation of catechol estrogens. Catechol estrogen 4-hydroxyestradiol (4-OHE2) is further oxidized to catechol estrogen-3,4-quinones, the major carcinogenic metabolites of estrogens. Evidence increasingly supports the critical role of 4-OHE2 in hormonal carcinogenesis via DNA adduct formation or production of reactive oxygen species, which finally contribute to the transformation of normal mammary epithelial cells and the enhanced growth of breast cancer cells. It is also reported that the level of 4-OHE2 or its quinones is highly up-regulated in urine or tissues of breast cancer patients. Thus, we highlight the oncogenic roles of 4-OHE2 in catechol estrogen-induced breast carcinogenesis.
Keywords : Breast cancer, Catechol estrogen-3,4-quinones, DNA adducts, 4-Hydroxyestradiol, Reactive oxygen species