Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells

Sujatha VENKATARAMAN; Xiaohong Jiang; Christine WEYDERT; Yuping Zhang; Hannah J ZHANG; Prabhat C GOSWAMI; Justine M RITCHIE; Larry W OBERLEY; Garry R BUETTNER

doi:10.1038/sj.onc.1208145

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Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells

Journal article

Peer reviewed

Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells

Sujatha VENKATARAMAN, Xiaohong Jiang, Christine WEYDERT, Yuping Zhang, Hannah J ZHANG, Prabhat C GOSWAMI, Justine M RITCHIE, Larry W OBERLEY and Garry R BUETTNER

Oncogene, Vol.24(1), pp.77-89

2005

DOI: 10.1038/sj.onc.1208145

PMID: 15543233

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Abstract

This study investigates the role of the antioxidant enzyme manganese superoxide dismutase (MnSOD) in androgen-independent human prostate cancer (PC-3) cells' growth rate in vitro and in vivo. MnSOD levels were found to be lower in parental PC-3 cells compared to nonmalignant, immortalized human prostate epithelial cells (P69SV40T). To unravel the role of MnSOD in the prostate cancer phenotype, PC-3 cells were stably transfected with MnSOD cDNA plasmid. The MnSOD protein and activity levels in clones overexpressing MnSOD were increased seven- to eightfold. These cell lines showed elongated cell doubling time, reduced anchorage-independent growth in soft agar compared to parental PC-3 (Wt) cells, and reduced growth rate of PC-3 tumor xenografts in athymic nude mice. Flow cytometric studies showed an increase in membrane potential in the MnSOD-overexpressing clone (Mn32) compared to Wt and Neo cells. Also, production of extracellular H2O2 was increased in the MnSOD-overexpressing clones. As determined by DNA cell cycle analysis, the proportion of cells in G1 phase was enhanced by MnSOD overexpression. Therefore, MnSOD not only regulates cell survival but also affects PC-3 cell proliferation by retarding G1 to S transition. Our results are consistent with MnSOD being a tumor suppressor gene in human prostate cancer.

Cell Physiology

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Molecular and cellular biology

Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes

Details

Title: Subtitle: Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells
Creators: Sujatha VENKATARAMAN - Free Radical and Radiation Biology Program - ESR Facility, University of Iowa, Iowa City, IA 52242-1101, United States
Xiaohong Jiang - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1101, United States
Christine WEYDERT - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1101, United States
Yuping Zhang - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1101, United States
Hannah J ZHANG - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1101, United States
Prabhat C GOSWAMI - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1101, United States
Justine M RITCHIE - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242-1101, United States
Larry W OBERLEY - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1101, United States
Garry R BUETTNER - Free Radical and Radiation Biology Program - ESR Facility, University of Iowa, Iowa City, IA 52242-1101, United States
Resource Type: Journal article
Publication Details: Oncogene, Vol.24(1), pp.77-89
Publisher: Nature Publishing; Basingstoke
DOI: 10.1038/sj.onc.1208145
PMID: 15543233
ISSN: 0950-9232
eISSN: 1476-5594
Language: English
Date published: 2005
Academic Unit: Radiation Oncology; Obstetrics and Gynecology
Record Identifier: 9984047651402771

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