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p44/42 MAP kinase-dependent regulation of catalase by autocrine human growth hormone protects human mammary carcinoma cells from oxidative stress-induced apoptosis

Oncogene volume 24, pages 3774–3785 (2005)Cite this article

Abstract

Previous microarray expression analyses have indicated autocrine human growth hormone (hGH) regulation of genes involved in the oxidative stress response. Expression analysis of antioxidant enzymes revealed that autocrine hGH increased both the mRNA and protein levels of catalase, superoxide dismutase 1 (SOD1), glutathione peroxidase and glutamylcysteine synthetase but not that of SOD2. As a consequence, autocrine hGH increased the antioxidant capacity of mammary carcinoma cells and protected against oxidative stress-induced apoptosis. Catalase activity was increased by autocrine production of hGH in mammary carcinoma cells and a catalase inhibitor abrogated protection from oxidative stress afforded by autocrine hGH. Autocrine hGH transcriptionally regulated catalase gene expression in a p44/42 MAP kinase-dependent manner and inhibition of MEK concordantly abrogated the protective effect of autocrine hGH against oxidative stress-induced apoptosis. Given that increased cellular oxidative stress is a key effector mechanism of specific chemotherapeutic agents, we propose that antagonism of autocrine hGH will improve the efficacy of chemotherapeutic regimes utilized for human mammary carcinoma.

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Acknowledgements

This work was supported by grants from the National Science and Technology Board of Singapore (to PEL), The School of Medicine Foundation (Bequest of Margaret Morley), University of Auckland (to PEL), The National Research Centre for Growth and Development, New Zealand (Theme 2) and The Marsden Fund, Royal Society of New Zealand (to PEL).

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Authors and Affiliations

  1. Department of Medicine, National University of Singapore, 30 Medical Dr., Singapore, 117609, Republic of Singapore

    Zhe Zhu & Kok-Onn Lee

  2. Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Dr., Singapore, 117609, Republic of Singapore

    Svetlana Mukhina

  3. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Tao Zhu

  4. CNRS UMR 5578, Physiologies Energetiques Cellulaires et Moléculaires, Université Claude Bernard, Lyon, 1, France

    Hichem C Mertani

  5. Liggins Institute and National Research Centre for Growth and Development, University of Auckland, 2-6 Park Avenue, Private Bag 92019, Auckland, New Zealand

    Peter E Lobie

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  1. Zhe Zhu
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Zhu, Z., Mukhina, S., Zhu, T. et al. p44/42 MAP kinase-dependent regulation of catalase by autocrine human growth hormone protects human mammary carcinoma cells from oxidative stress-induced apoptosis. Oncogene 24, 3774–3785 (2005). https://doi.org/10.1038/sj.onc.1208541

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