RGD Reference Report - Manganese superoxide dismutase is a p53-regulated gene that switches cancers between early and advanced stages. - Rat Genome Database

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Manganese superoxide dismutase is a p53-regulated gene that switches cancers between early and advanced stages.

Authors: Dhar, SK  Tangpong, J  Chaiswing, L  Oberley, TD  St Clair, DK 
Citation: Dhar SK, etal., Cancer Res. 2011 Nov 1;71(21):6684-95. doi: 10.1158/0008-5472.CAN-11-1233. Epub 2011 Oct 18.
RGD ID: 8547525
Pubmed: PMID:22009531   (View Abstract at PubMed)
PMCID: PMC3206134   (View Article at PubMed Central)
DOI: DOI:10.1158/0008-5472.CAN-11-1233   (Journal Full-text)

Manganese superoxide dismutase (MnSOD) plays a critical role in the survival of aerobic life, and its aberrant expression has been implicated in carcinogenesis and tumor resistance to therapy. However, despite extensive studies in MnSOD regulation and its role in cancer, when and how the alteration of MnSOD expression occurs during the process of tumor development in vivo are unknown. Here, we generated transgenic mice expressing a luciferase reporter gene under the control of human MnSOD promoter-enhancer elements and investigated the changes of MnSOD transcription using the 7,12-dimethylbenz(alpha)anthracene (DMBA)/12-O-tetradecanoylphorbol-l3-acetate (TPA) multistage skin carcinogenesis model. The results show that MnSOD expression was suppressed at a very early stage but increased at late stages of skin carcinogenesis. The suppression and subsequent restoration of MnSOD expression were mediated by two transcription-factors, Sp1 and p53. Exposure to DMBA and TPA activated p53 and decreased MnSOD expression via p53-mediated suppression of Sp1 binding to the MnSOD promoter in normal-appearing skin and benign papillomas. In squamous cell carcinomas, Sp1 binding increased because of the loss of functional p53. We used chromatin immunoprecipitation, electrophoretic mobility shift assay, and both knockdown and overexpression of Sp1 and p53 to verify their roles in the expression of MnSOD at each stage of cancer development. The results identify MnSOD as a p53-regulated gene that switches between early and advanced stages of cancer. These findings also provide strong support for the development of means to reactivate p53 for the prevention of tumor progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Skin Neoplasms disease_progressionISOSod2 (Mus musculus)8547525; 8547525 RGD 
Skin Neoplasms disease_progressionIEP 8547525 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod2  (superoxide dismutase 2)

Genes (Mus musculus)
Sod2  (superoxide dismutase 2, mitochondrial)

Genes (Homo sapiens)
SOD2  (superoxide dismutase 2)


Additional Information