TY - JOUR
T1 - Mitochondrial manganese-superoxide dismutase expression in ovarian cancer
T2 - Role in cell proliferation and response to oxidative stress
AU - Hu, Yumin
AU - Rosen, Daniel G.
AU - Zhou, Yan
AU - Feng, Li
AU - Yang, Gong
AU - Liu, Jinsong
AU - Huang, Peng
PY - 2005/11/25
Y1 - 2005/11/25
N2 - 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 O 2- 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.
AB - 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 O 2- 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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U2 - 10.1074/jbc.M503296200
DO - 10.1074/jbc.M503296200
M3 - Article
C2 - 16179351
AN - SCOPUS:28244447656
SN - 0021-9258
VL - 280
SP - 39485
EP - 39492
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 47
ER -