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PMID:16179351

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Citation

Hu, Y, Rosen, DG, Zhou, Y, Feng, L, Yang, G, Liu, J and Huang, P (2005) Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress. J. Biol. Chem. 280:39485-92

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.

Links

PubMed Online version:10.1074/jbc.M503296200

Keywords

Animals; Base Sequence; Cell Line, Tumor; Cell Proliferation; Cystadenoma/enzymology; Cystadenoma/genetics; Cystadenoma/pathology; Female; Gene Expression Profiling; Humans; Mice; Mitochondria/enzymology; Oligonucleotide Array Sequence Analysis; Ovarian Neoplasms/enzymology; Ovarian Neoplasms/genetics; Ovarian Neoplasms/pathology; Ovary/cytology; Ovary/enzymology; Oxidative Stress; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA, Neoplasm/genetics; RNA, Neoplasm/metabolism; RNA, Small Interfering/genetics; Superoxide Dismutase/genetics; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SODM

involved_in

GO:0000303: response to superoxide

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SODM

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SODM

involved_in

GO:0019430: removal of superoxide radicals

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SODM

involved_in

GO:0032364: oxygen homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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