Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome

Jonna Frasor, Edmund C. Chang, Barry Komm, Chin Yo Lin, Vinsensius B. Vega, Edison T. Liu, Lance D. Miller, Johanna Smeds, Jonas Bergh, Benita S. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

The beneficial effect of the selective estrogen receptor (ER) modulator tamoxifen in the treatment and prevention of breast cancer is assumed to be through its ability to antagonize the stimulatory actions of estrogen, although tamoxifen can also have some estrogen-like agonist effects. Here, we report that, in addition to these mixed agonist/antagonist actions, tamoxifen can also selectively regulate a unique set of >60 genes, which are minimally regulated by estradiol (E2) or raloxifene in ERα-positive MCF-7 human breast cancer cells. This gene regulation by tamoxifen is mediated by ERα and reversed by E2 or ICI 182,780. Introduction of ERβ into MCF-7 cells reverses tamoxifen action on ∼75% of these genes. To examine whether these genes might serve as markers of tamoxifen sensitivity and/or the development of resistance, their expression level was examined in breast cancers of women who had received adjuvant therapy with tamoxifen. High expression of two of the tamoxifen-stimulated genes, YWHAZ/14-3-3z and LOC441453, was found to correlate significantly with disease recurrence following tamoxifen treatment in women with ER-positive cancers and hence seem to be markers of a poor prognosis. Our data indicate a new dimension in tamoxifen action, involving gene expression regulation that is tamoxifen preferential, and identify genes that might serve as markers of tumor responsiveness or resistance to tamoxifen therapy. This may have a potential effect on the choice of tamoxifen versus aromatase inhibitors as adjuvant endocrine therapy.

Original languageEnglish (US)
Pages (from-to)7334-7340
Number of pages7
JournalCancer Research
Volume66
Issue number14
DOIs
StatePublished - Jul 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Frasor, J., Chang, E. C., Komm, B., Lin, C. Y., Vega, V. B., Liu, E. T., Miller, L. D., Smeds, J., Bergh, J., & Katzenellenbogen, B. S. (2006). Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Research, 66(14), 7334-7340. https://doi.org/10.1158/0008-5472.CAN-05-4269