Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1
Copyright policy )Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1
Increased expression of mac25/insulin-like growth factor binding-protein related protein-1 (IGFBP-rP1) in human breast and prostate epithelial cell lines results in the suppression of tumor growth. CDNA expression array analysis revealed increased manganese superoxide dismutase (SOD-2) expression in the mac25/IGFBP-rP1-transfected M12 human prostate cancer cell line compared to M12 control cells. SOD-2 has been postulated to be a tumor suppressor. SOD-2 was also increased in LNCaP cells stably transfected with mac25/IGFBP-rP1, but not in mac25/IGFBP-rP1-transfected PC-3 cells. Mac25 LNCaP cells had a marked decrease in tumor growth in nude mice compared to controls, but there was no difference in tumor growth in mac25 PC-3 cells compared to control. Phosphorylated Erk and Akt were increased in the M12 and LNCaP transfected mac25/IGFBP-rP1 cells but not PC-3 mac25. Inhibition of PI-3 kinase results in a marked decrease in viability of the M12-mac25 cells compared to M12 controls. Cells treated with H(2)O(2) result in an increase in phospho-ERK. Transfection of SOD-2 in M12 cells markedly decreased tumor growth, apoptosis, G1 delay in the cell cycle, and expression of senescence associated beta-galactosidase. These results suggest that one of the downstream mediators of the senescence-associated tumor suppression effect of mac25/IGFBP-rP1 is SOD-2.
- University of Wisconsin–Oshkosh United States
- Fred Hutchinson Cancer Research Center South Africa
- William S. Middleton Memorial Veterans Hospital United States
- University of Mary United States
- University of Iowa Health Alliance United States
Male, MAP Kinase Signaling System, Morpholines, G1 Phase, Mice, Nude, Apoptosis, Hydrogen Peroxide, Adenocarcinoma, Gene Expression Regulation, Neoplastic, Insulin-Like Growth Factor Binding Proteins, Mice, Chromones, Enzyme Induction, Animals, Humans, Enzyme Inhibitors, Mitogen-Activated Protein Kinases, Carrier Proteins, Cellular Senescence, Cell Line, Transformed
Male, MAP Kinase Signaling System, Morpholines, G1 Phase, Mice, Nude, Apoptosis, Hydrogen Peroxide, Adenocarcinoma, Gene Expression Regulation, Neoplastic, Insulin-Like Growth Factor Binding Proteins, Mice, Chromones, Enzyme Induction, Animals, Humans, Enzyme Inhibitors, Mitogen-Activated Protein Kinases, Carrier Proteins, Cellular Senescence, Cell Line, Transformed
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