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PMID: 17192397 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Integrated molecular profiling of SOD2 expression in multiple myeloma.

Blood ·Vol. 109 ·No. 9 ·2007-05-01 ·Pages 3953-62

Hurt EM, Thomas SB, Peng B, Farrar WL

Abstract

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 compared with healthy donors. Overexpression 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.

MeSH Terms
2-Methoxyestradiol Animals Apoptosis/drug effects,genetics Cell Line, Tumor DNA Damage/drug effects,genetics Estradiol/analogs & derivatives,pharmacology Gene Expression Regulation, Enzymologic/drug effects,genetics Gene Expression Regulation, Neoplastic/drug effects,genetics Humans Multiple Myeloma/enzymology,genetics Neoplasm Proteins/biosynthesis,genetics Proteomics Reactive Oxygen Species Signal Transduction/drug effects,genetics Superoxide Dismutase/biosynthesis,genetics Tubulin Modulators/pharmacology
Chemicals
Neoplasm Proteins Reactive Oxygen Species Tubulin Modulators Estradiol 2-Methoxyestradiol Superoxide Dismutase superoxide dismutase 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hurt Elaine M
Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA.
Thomas Suneetha B
Peng Benjamin
Farrar William L
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-07-035162
Published
2007-05-01
Epub
2006-00-27
Pages
3953-62
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1874573
Subset
IM
Grants
NCI NIH HHS · N01CO12400 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-07-035162 PMC Full Text View journal details
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