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Glutathione Peroxidase 2 and Its Role in Cancer

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Selenium

Abstract

Glutathione peroxidase 2 (GPx2) is preferentially expressed in the intestine, but also upregulated in malignant epithelial cells of other organs. Whether this upregulation is beneficial or detrimental for cancer cell growth and thus for the outcome of cancer, is unclear. The localization of GPx2 in the crypt bases of the intestine, where stem cells proliferate under the control of the Wnt pathway, points to a role in the self-renewal of the intestinal mucosa. This assumption is supported by the fact that GPx2 is a target of the Wnt pathway. In GPx2 knockout mice, apoptosis is highly increased in crypt bases corroborating an involvement of GPx2 in mucosal homeostasis. So far, the role of GPx2 appears to be pro-carcinogenic either by supporting cancer cells to escape apoptosis or by directly maintaining proliferation. On the other hand, GPx2 is induced by Nrf2 transcription factor which is generally accepted to induce endogenous defense systems. In addition, GPx2 counteracts COX-2 expression, thereby decreasing inflammation and migration of tumor cells. Collectively, the role of GPx2 may depend on the stage of cancer. GPx2 likely inhibits the initiation of cancer triggered either by oxidative damage or chronic inflammation and might prevent invasiveness and metastasis, but supports progression of established tumors. Evidences for this dual role of GPx2 are presented and discussed.

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Author information

Authors and Affiliations

  1. Biochemical Institute, Justus Liebig University Giessen, Friedrichstr. 24, 35392, Giessen, Germany

    Antje Banning

  2. Department Biochemistry of Micronutrients, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany

    Antje Banning, Anna Kipp & Regina Brigelius-Flohé

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  1. Antje Banning
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  2. Anna Kipp
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  3. Regina Brigelius-Flohé
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Corresponding author

Correspondence to Regina Brigelius-Flohé .

Editor information

Editors and Affiliations

  1. National Cancer Institute, Basic Research Laboratory, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Dolph L. Hatfield

  2. University of Hawaii, Monoa, Dole Street 2444, Honolulu, 96822, Hawaii, USA

    Marla J. Berry

  3. , Division of Genetics, Department of Medi, Brigham and Women’s Hospital and Harvard, Avenue Louis Pasteur 77, Boston, 02115, USA

    Vadim N. Gladyshev

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Banning, A., Kipp, A., Brigelius-Flohé, R. (2011). Glutathione Peroxidase 2 and Its Role in Cancer. In: Hatfield, D., Berry, M., Gladyshev, V. (eds) Selenium. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1025-6_21

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