ABSTRACT Manganese superoxide dismutase (MnSOD) has been shown to play an important role in preventing the development of cancer. MnSOD activity is reduced in many transformed cells and

tumor tissues. We previously showed that the reduced level of MnSOD activity in cancer cells was not due to a defect in the primary structure of MnSOD protein, but rather was due to defects

in gene expression. To elucidate the cause for the reduced expression of human MnSOD in cancer, we investigated the nucleotide sequence in the regulatory region of the MnSOD gene in a normal

human cell line and various human tumor cell lines. A DNA fragment spanning 3.4 kb 5′ flanking region of the MnSOD gene isolated from a normal human genomic DNA library was used to

the binding pattern of AP-2 and lead to a reduction in transcription activity using a luciferase reporter assay system. These results suggest that the reduced level of MnSOD expression in

some tumor cells is, at least in part, due to a defect in the DNA sequence of the promoter region. Access through your institution Buy or subscribe This is a preview of subscription content,

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Download references ACKNOWLEDGEMENTS We thank Dr H-C Yen for statistical assistance. This work was supported by NIH grants CA 49797, CA 59835, and HL 03544, and grants from the American

Heart association and the Environmental Protection Agency to DK St.Clair. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Graduate Center for Toxicology, University of Kentucky, Lexington,

40536-0305, Kentucky, USA Yong Xu, Anuradha Krishnan, X Steven Wan, Hideyuki Majima, Che-Chung Yeh, Gabriele Ludewig, Edward J Kasarskis & Daret K St.Clair * Department of Neurology,

University of Kentucky, Lexington, 40536-0305, Kentucky, USA Yong Xu, Anuradha Krishnan, X Steven Wan, Hideyuki Majima & Edward J Kasarskis Authors * Yong Xu View author publications You

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cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells. _Oncogene_ 18, 93–102 (1999). https://doi.org/10.1038/sj.onc.1202265 Download citation *

Received: 20 April 1998 * Revised: 02 July 1998 * Accepted: 03 July 1998 * Published: 19 January 1999 * Issue Date: 07 January 1999 * DOI: https://doi.org/10.1038/sj.onc.1202265 SHARE THIS

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Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * tumor suppressor gene * mutation * promoter * transcription factors * MnSOD * reactive oxygen species