title: Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress.
abstract: Superoxide dismutases (SODs) are important antioxidant enzymes responsible for the elimination of superoxide radical (O(2)(-)). 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 O(2)(-) 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.
authors.affiliation: Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Hu
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rosen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003537:Cystadenoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000166:cytology / Q000201:enzymology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase