P44/42 map kinase-dependent regulation of catalase by autocrine human growth hormone protects human mammary carcinoma cells from oxidative stress-induced apoptosis

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. Access through your institution Buy or subscribe This is a preview of subscription content,

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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). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medicine, National University of Singapore, 30 Medical Dr.,

Singapore, 117609, Republic of Singapore Zhe Zhu & Kok-Onn Lee * Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Dr., Singapore, 117609, Republic

of Singapore Svetlana Mukhina * The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA Tao Zhu * CNRS UMR 5578, Physiologies

Energetiques Cellulaires et Moléculaires, Université Claude Bernard, Lyon, 1, France Hichem C Mertani * 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 Authors * Zhe Zhu View author publications You can also search for this author inPubMed Google Scholar *

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ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 06 December 2004 * Revised: 05 January 2005 *

Accepted: 05 January 2005 * Published: 14 March 2005 * Issue Date: 26 May 2005 * DOI: https://doi.org/10.1038/sj.onc.1208541 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * growth hormone * autocrine * mammary carcinoma * oxidative stress * catalase