IMR Press / FBL / Volume 10 / Issue 2 / DOI: 10.2741/1630

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Estrogen receptor regulation of quinone reductase in breast cancer: implications for estrogen-induced breast tumor growth and therapeutic uses of tamoxifen
Show Less
1 Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44122, USA
2 Department of Molecular and Integrative Physiology, University of Illinois and College of Medicine, Urbana, IL 61801

Academic Editor: Subrata Haldar

Front. Biosci. (Landmark Ed) 2005, 10(2), 1440–1461; https://doi.org/10.2741/1630
Published: 1 May 2005
Abstract

Antiestrogens have found widespread use in the treatment of breast cancer (reviewed in ref. 1). There is also interest in the use of tamoxifen as a preventive agent for breast cancer. However, the mechanism for the antitumor effects of antiestrogens is relatively unknown. For the most part it is thought that the basis for the anticancer action of antiestrogens is the inhibition of estradiol (E2)-stimulated tumor growth. We have observed however that antiestrogens can activate detoxifying enzymes, like quinone reductase (NQO1), which protect cells against the toxic and tumor-promoting effects of carcinogens (2). Studies characterizing the molecular mechanisms behind the regulation of NQO1 by the Estrogen Receptor (ER) support an important role of the ER in pathways regulating antioxidant defenses. Moreover these findings represent a novel mechanism through which antiestrogens function. The activation of NQO1 may contribute to the beneficial anticancer and antioxidant activity of antiestrogens in breast cancer and possibly other estrogen target tissues. It is possible that the basis for some of the anticancer action of antiestrogens is that the induction of NQO1 inhibits the genotoxic effects induced by the oxidative metabolism of estrogens.

Keywords
Estrogens
Estrogen receptor
Antiestrogens
Quinone reductase
Review
Share
Back to top