Protective roles of quinone reductase and tamoxifen against estrogen-induced mammary tumorigenesis

M. M. Montano, L. J. Chaplin, H. Deng, S. Mesia-Vela, N. Gaikwad, M. Zahid, E. Rogan

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

We previously reported that antiestrogen-liganded estrogen receptor β (ERβ) transcriptionally activates the major detoxifying enzyme quinone reductase (QR) (NAD(P)H:quinone oxidoreductase). Further studies on the functional role of ERβ-mediated upregulation of antioxidative enzymes indicated protective effects against estrogen-induced oxidative DNA damage (ODD). We now report on in vivo and in vitro studies that show that ERβ-mediated upregulation of QR are involved in the protection against estrogen-induced mammary tumorigenesis. Using the August Copenhagen Irish (ACI) model of estrogen-induced carcinogenesis, we observed that increased ODD and decreased QR expression occur early in the process of estrogen-induced mammary tumorigenesis. Prevention of ACI mammary gland tumorigenesis by tamoxifen was accompanied by decreased ODD and increased QR levels. These correlative findings were supported by our findings that downregulation of QR levels led to increased levels of estrogen quinone metabolites and enhanced transformation potential of 17β-estradiol treated MCF10A non-tumorigenic breast epithelial cells. Concurrent expression of ERβ and treatment with 4-hydroxytamoxifen decreased tumorigenic potential of these MCF10A cells. We conclude that upregulation of QR, through induction by tamoxifen, can inhibit estrogen-induced ODD and mammary cell tumorigenesis, representing a possible novel mechanism of tamoxifen prevention against breast cancer.

Original languageEnglish (US)
Pages (from-to)3587-3590
Number of pages4
JournalOncogene
Volume26
Issue number24
DOIs
StatePublished - May 24 2007
Externally publishedYes

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Keywords

  • Antiestrogens
  • Estrogen
  • Estrogen receptor β
  • Mammary gland
  • Oxidative damage
  • Quinone reductase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Montano, M. M., Chaplin, L. J., Deng, H., Mesia-Vela, S., Gaikwad, N., Zahid, M., & Rogan, E. (2007). Protective roles of quinone reductase and tamoxifen against estrogen-induced mammary tumorigenesis. Oncogene, 26(24), 3587-3590. https://doi.org/10.1038/sj.onc.1210144