Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells

Yong Xu; Anuradha Krishnan; X Steven Wan; Hideyuki Majima; Che-Chung Yeh; Gabriele Ludewig; Edward J Kasarskis; Daret K St.Clair

doi:10.1038/sj.onc.1202265

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Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells

Journal article

Peer reviewed

Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells

Yong Xu, Anuradha Krishnan, X Steven Wan, Hideyuki Majima, Che-Chung Yeh, Gabriele Ludewig, Edward J Kasarskis and Daret K St.Clair

Oncogene, Vol.18(1), pp.93-102

01/1999

DOI: 10.1038/sj.onc.1202265

PMID: 9926924

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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 determine the DNA sequence of MnSOD promoter. PCR primers were used for amplification of the 3.4 kb 5′ flanking region of the human MnSOD gene in cancer cells. Sequence analysis identified three heterozygous mutations in the proximal region of the promoter in five human tumor cell lines. These mutations, clustered around the GC-rich region of the human MnSOD promoter, change 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.

Details

Title: Subtitle: Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells
Creators: Yong Xu
Anuradha Krishnan
X Steven Wan
Hideyuki Majima
Che-Chung Yeh
Gabriele Ludewig
Edward J Kasarskis
Daret K St.Clair
Resource Type: Journal article
Publication Details: Oncogene, Vol.18(1), pp.93-102
DOI: 10.1038/sj.onc.1202265
PMID: 9926924
ISSN: 0950-9232
eISSN: 1476-5594
Language: English
Date published: 01/1999
Academic Unit: Occupational and Environmental Health
Record Identifier: 9983997331402771

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