[Frontiers in Bioscience 10, 1440-1461 May 1, 2005] 1440 ESTROGEN RECEPTOR REGULATION OF QUINONE REDUCTASE IN BREAST CANCER: IMPLICATIONS FOR ESTROGEN-INDUCED BREAST TUMOR GROWTH AND THE THERAPEUTIC USES OF TAMOXIFEN

1. Abstract 2. Introduction 2.1. Estrogen receptor (ER) bioactivity in breast cancer cells 2.2. ER alpha and beta 2.3. Antiestrogens and the regulation of ER bioactivity in breast cancer cells 2.4. Detoxifying enzymes and chemoprotection against cancer 2.5. Regulation of the expression of detoxifying enzymes 2.6. Metabolism of estrogens 2.7. Role of estrogen metabolites in carcinogenesis 3. Regulation of NQO1 by the ER 3.1. Induction of NQO1 activity in breast cancer cells by antiestrogens 3.2. Induction of EpRE enhancer activity by antiestrogens in breast cancer cells 3.3. Regulation of NQO1 gene transcriptional activity by ER-alpha and ER-beta 3.4. Analysis of the interaction of ER-alpha and ER-beta with the EpRE 3.5. Identification of a novel protein factor, hPMC2, involved in the regulation of NQO1 activity by the ER 4. Functional implications of antiestrogen regulation of NQO1: protection against estrogeninduced DNA damage 4.1. Physiological levels of estrogens induce DNA damage independent of E and dependent on estrogen metabolism 4.2. Role of NQO1 and ER-beta in antiestrogen inhibition of estrogen-induced DNA damage 5. Perspective 6. Acknowledgements 7. References