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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

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Abstract

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 H2O2 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 β-galactosidase. These results suggest that one of the downstream mediators of the senescence-associated tumor suppression effect of mac25/IGFBP-rP1 is SOD-2.

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Acknowledgements

The study was supported by the Veterans Affairs Research Service and DOD to SRP and TDO, and NIH DK52683 and PO1-CA 85859 to SRP.

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Authors and Affiliations

  1. Veterans Affairs Puget Sound Health Care System, University of Washington School of Medicine, Seattle, 98105, WA, USA

    Stephen R Plymate, Kathy H Haugk, Marie K Tennant & Rolf Drivdahl

  2. Department of Medicine, University of Washington School of Medicine, Seattle, 98105, WA, USA

    Stephen R Plymate & Peter S Nelson

  3. Department of Molecular and Cell Biology Program, University of Washington School of Medicine, Seattle, 98105, WA, USA

    Cynthia C Sprenger

  4. Fred Hutchinson Cancer Research Center, Seattle, 98107, WA, USA

    Peter S Nelson

  5. Department of Radiology, University of IA, Iowa City, 52242, IA, USA

    Yuping Zhang & Larry W Oberley

  6. Department of Pathology and Laboratory Medicine, University of WI, Madison, 53705, WI, USA

    Weixiong Zhong & Terry D Oberley

  7. Pathology Service, William S Middleton Memorial Veterans Hospital, Madison, 53705, WI, USA

    Weixiong Zhong & Terry D Oberley

Authors
  1. Stephen R Plymate
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  2. Kathy H Haugk
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  3. Cynthia C Sprenger
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  4. Peter S Nelson
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  5. Marie K Tennant
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  6. Yuping Zhang
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  7. Larry W Oberley
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  8. Weixiong Zhong
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  9. Rolf Drivdahl
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  10. Terry D Oberley
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Correspondence to Stephen R Plymate.

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Plymate, S., Haugk, K., Sprenger, C. et al. 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. Oncogene 22, 1024–1034 (2003). https://doi.org/10.1038/sj.onc.1206210

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  • DOI: https://doi.org/10.1038/sj.onc.1206210

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