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Tamoxifen enhances interferon-regulated gene expression in breast cancer cells

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Abstract

The molecular basis for the enhanced growth inhibition of MCF-7 human breast cancer xenografts by a combination of human interferon-β (IFN-β) and tamoxifen was investigated. Treatment of MCF-7, MDA-MB-231, and BT-20 cells with the combination of IFN-β and tamoxifen resulted in enhanced antiproliferative effects in vitro. Treatment with the combination of IFN-β and tamoxifen enhanced the expression of several IFN-β-inducible genes in human breast carcinoma cell lines relative to levels induced by IFN-β alone. Tamoxifen alone did not induce transcription of IFN-stimulated genes (ISGs). Augmentation of ISG expression by the combination of IFN-β and tamoxifen was noted in breast tumor cell lines irrespective of their functional estrogen receptor (ER) status or their dependence on estradiol for growth, suggesting that upregulation of ISGs was independent of ER status. Enhancement of IFN-stimulated gene expression by tamoxifen occurred at the transcripti onal level. Expression of transfected reporter genes under the control of IFN-α/β regulated promoters was also enhanced in IFN-β and tamoxifen-treated cells. Similarly, transcriptional induction of chimeric reporter plasmids driven by an IFN-γ inducible promoter (GAS; IFN-γ activated site) was also enhanced by the combination of IFN-γ and tamoxifen. In tamoxifen treated cells, IFN-β and IFN-γ readily activated transcription factors ISGF-3 and GAF, respectively. Therefore, augmentation of ISG expression by tamoxifen is an early event in the antitumoral activity of this drug combination. (Mol Cell Biochem 167: 169-177, 1997)

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Authors and Affiliations

  1. Departments of Microbiology and Immunology, University of Maryland Cancer Center, Baltimore, MD, 21201, USA

    Daniel J. Lindner, Venkatadri Kolla, Dhananjaya V. Kalvakolanu & Ernest C. Borden

  2. Department of Medicine, University of Maryland Cancer Center, Baltimore, MD, 21201, USA

    Dhananjaya V. Kalvakolanu & Ernest C. Borden

  3. Department of Pharmacology, University of Maryland Cancer Center, Baltimore, MD, 21201, USA

    Ernest C. Borden

  4. Program in Oncology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Dhananjaya V. Kalvakolanu & Ernest C. Borden

  5. Molecular and Cell Biology Program, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Dhananjaya V. Kalvakolanu

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Lindner, D.J., Kolla, V., Kalvakolanu, D.V. et al. Tamoxifen enhances interferon-regulated gene expression in breast cancer cells. Mol Cell Biochem 167, 169–177 (1997). https://doi.org/10.1023/A:1006854110122

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