MnSOD Up-Regulates Maspin Tumor Suppressor Gene Expression in Human Breast and Prostate Cancer Cells

Hong Duan, Hannah J. Zhang, Ji Qin Yang, Larry W. Oberley, Bernard W Futscher, Frederick E. Domann

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme with tumor suppressor activity; however, the molecular mechanisms of MnSOD antitumor effects remain unclear. We hypothesized that MnSOD activity in cancer cells might cause downstream changes in the expression of other tumor suppressor genes. To determine whether maspin, a tumor suppressor gene that inhibits breast cancer cell invasion and metastasis, might be a target of MnSOD, we forced MnSOD expression in several human breast and prostate cancer cell lines by adenovirus-mediated gene transfer and measured maspin mRNA expression. Forced expression of MnSOD caused maspin mRNA to accumulate in a dose-dependent manner in both human breast and prostate cancer cells. Normal p53 was not necessary to mediate the effect of MnSOD because MnSOD up-regulated maspin in cells that harbor wild-type p53 and in cells that harbor mutant p53. Moreover, the effects of MnSOD on maspin were not due to demethylation of the maspin promoter. Analyses of maspin promoter activity, transcriptional run-on, and mRNA stability showed that maspin mRNA stability was the major mechanism for maspin up-regulation by MnSOD. Our findings identify a mechanism underlying MnSOD antitumor effects and provide evidence to support MnSOD as a genetic therapy in the treatment of human breast and prostate cancers.

Original languageEnglish (US)
Pages (from-to)677-688
Number of pages12
JournalAntioxidants and Redox Signaling
Volume5
Issue number5
StatePublished - Oct 2003

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Tumor Suppressor Genes
Gene expression
Superoxide Dismutase
Tumors
Prostatic Neoplasms
Up-Regulation
Cells
Breast Neoplasms
Gene Expression
Messenger RNA
RNA Stability
Ports and harbors
SERPIN-B5
Genes
Gene transfer
Adenoviridae
Genetic Therapy
Neoplasms
Antioxidants
Neoplasm Metastasis

ASJC Scopus subject areas

  • Biochemistry

Cite this

MnSOD Up-Regulates Maspin Tumor Suppressor Gene Expression in Human Breast and Prostate Cancer Cells. / Duan, Hong; Zhang, Hannah J.; Yang, Ji Qin; Oberley, Larry W.; Futscher, Bernard W; Domann, Frederick E.

In: Antioxidants and Redox Signaling, Vol. 5, No. 5, 10.2003, p. 677-688.

Research output: Contribution to journalArticle

Duan, Hong ; Zhang, Hannah J. ; Yang, Ji Qin ; Oberley, Larry W. ; Futscher, Bernard W ; Domann, Frederick E. / MnSOD Up-Regulates Maspin Tumor Suppressor Gene Expression in Human Breast and Prostate Cancer Cells. In: Antioxidants and Redox Signaling. 2003 ; Vol. 5, No. 5. pp. 677-688.
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