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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3953-3962. Prepublished online as a Blood First Edition Paper on December 27, 2006; DOI 10.1182/blood-2006-07-035162. This Article Full Text (PDF) Supplemental Methods and Tables All Versions of this Article: blood-2006-07-035162v1 109/9/3953    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hurt, E. M Articles by Farrar, W. L Search for Related Content PubMed PubMed Citation Articles by Hurt, E. M Articles by Farrar, W. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2006 Accepted December 18, 2006 Integrated molecular profiling of SOD2 expression in multiple myeloma Elaine M Hurt*, Suneetha B Thomas, Benjamin Peng, and William L Farrar Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, NCI-Frederick, NIH, Frederick, MD, United States Basic Research Program, SAIC-Frederick, NCI, Frederick, MD, United States School of Dental Sciences, University of Melbourne, Melbourne, Australia * Corresponding author; email: hurte{at}ncifcrf.gov. Reactive oxygen species are known to be involved in several cellular processes, including cell signaling. SOD2 is a key enzyme in the conversion of reactive oxygen species and has been implicated in a host of disease states including cancer. Using an integrated, whole cell approach encompassing epigenetics, genomics and proteomics we have defined the role of SOD2 in multiple myeloma. We show that the SOD2 promoter is methylated in several cell lines and there is a correlative decrease in expression. Furthermore, myeloma patient samples have decreased SOD2 expression as compared to normal donors. Over-expression of SOD2 results in decreased proliferation and altered sensitivity to 2-methoxyestradiol-induced DNA damage and apoptosis. Genomic profiling revealed regulation of 65 genes, including genes involved in tumorigenesis, and proteomic analysis identified activation of the JAK/STAT pathway. Analysis of nearly 400 activated transcription factors identified 31 transcription factors with altered DNA binding activity, including XBP1, NFAT, forkhead, and GAS binding sites. Integration of data from our gestalt molecular analysis has defined a role for SOD2 in cellular proliferation, JAK/STAT signaling, and regulation of several transcription factors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Sharifi, E. M. Hurt, S. B. Thomas, and W. L. Farrar Effects of Manganese Superoxide Dismutase Silencing on Androgen Receptor Function and Gene Regulation: Implications for Castration-Resistant Prostate Cancer Clin. Cancer Res., October 1, 2008; 14(19): 6073 - 6080. [Abstract] [Full Text] [PDF]

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