Journal of Biological Chemistry
Volume 280, Issue 47, 25 November 2005, Pages 39485-39492
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Mechanisms of Signal Transduction
Mitochondrial Manganese-Superoxide Dismutase Expression in Ovarian Cancer: ROLE IN CELL PROLIFERATION AND RESPONSE TO OXIDATIVE STRESS*

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Superoxide dismutases (SODs) are important antioxidant enzymes responsible for the elimination of superoxide radical (O2). The manganese-containing SOD (Mn-SOD) has been suggested to have tumor suppressor function and is located in the mitochondria where the majority of O2 is generated during respiration. Although increased reactive oxygen species (ROS) in cancer cells has long been recognized, the expression of Mn-SOD in cancer and its role in cancer development remain elusive. The present study used a human tissue microarray to analyze Mn-SOD expression in primary ovarian cancer tissues, benign ovarian lesions, and normal ovary epithelium. Significantly higher levels of Mn-SOD protein expression were detected in the malignant tissues compared with normal tissues (p < 0.05). In experimental systems, suppression of Mn-SOD expression by small interfering RNA caused a 70% increase of superoxide in ovarian cancer cells, leading to stimulation of cell proliferation in vitro and more aggressive tumor growth in vivo. Furthermore, stimulation of mitochondrial O2 production induced an increase of Mn-SOD expression. Our findings suggest that the increase in Mn-SOD expression in ovarian cancer is a cellular response to intrinsic ROS stress and that scavenging of superoxide by SOD may alleviate the ROS stress and thus reduce the simulating effect of ROS on cell growth.

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*

This study was supported in part by Grants CA85563, CA100428, and CA109041 (to P. H.) from the NCI, National Institutes of Health, and RSG-04-028-1-CCE (to J. L.) from the American Cancer Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

These authors contributed equally to this work.

2

Recipient of the Rosalie B. Hite Fellowship.