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Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

Leukemia volume 25, pages 1103–1110 (2011)Cite this article

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Abstract

Estrogen receptor β (ERβ) is expressed in immune cells and studies have suggested an antiproliferative function of ERβ. We detected ERβ expression in murine T- and human B-cell lymphoma cell lines and analyzed the effects of estradiol and selective ERβ agonists on lymphoma growth in culture and in vivo. Treating the cells with estradiol had minor effects on cell growth, whereas the selective ERβ agonists diarylpropionitrile (DPN) and KB9520 showed a strong antiproliferative effect. When grafting mice with murine T-cell lymphoma cells, male mice developed larger tumors compared with female mice, a difference that was abolished following ovariectomy, showing estrogen-dependent growth in vivo. To investigate whether lymphoma growth may be inhibited in vivo by ERβ agonist treatment, mice grafted with murine lymphoma cells were treated with DPN or KB9520. Both ERβ-selective agonists strongly inhibited lymphoma growth. The reduced tumor size seen following either DPN or KB9520 treatment was due to reduced proliferation and increased apoptosis. Our results show an ERβ ligand-dependent antiproliferative effect of lymphoma cells expressing endogenous ERβ and that lymphoma cell growth in vivo can efficiently be inhibited by ERβ agonists. This suggests that ERβ agonists may be useful in the treatment of lymphomas.

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Acknowledgements

Jan-Åke Gustafsson and collaborators are acknowledged for providing chicken ERβ 503 antibody. Anders Ström is acknowledged for providing CMV-FLAG-ERα and CMV-FLAG-ERβ expression vectors. This work was supported by grants to SO from the Swedish Cancer Society, the European Union FP7 project TOLERAGE (HEALTH-F4-2008-202156) and the Karo Bio Research Foundation.

Author Contributions

KY designed and performed research, analyzed data and wrote the manuscript; MI and MSH performed research and analyzed data; PR and SN advised on research and made critical comments on the manuscript; MJ advised on research, provided research support and made critical comments on the manuscript; SO designed and led the research, provided research support and made critical comments on the manuscript.

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Authors and Affiliations

  1. Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden,

    K Yakimchuk, M Iravani, M S Hasni & S Okret

  2. Karo Bio AB, Novum, Huddinge, Sweden,

    P Rhönnstad & S Nilsson

  3. Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden

    M Jondal

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  1. K Yakimchuk
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Correspondence to S Okret.

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The authors declare no conflict of interest. Patrik Rhönnstad and Stefan Nilsson are employed by Karo Bio AB.

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Yakimchuk, K., Iravani, M., Hasni, M. et al. Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo. Leukemia 25, 1103–1110 (2011). https://doi.org/10.1038/leu.2011.68

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