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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2004-6-2
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pubmed:abstractText |
The IL-12Rbeta2 gene is expressed in human mature B cell subsets but not in transformed B cell lines. Silencing of this gene may be advantageous to neoplastic B cells. Our objective was to investigate the mechanism(s) and the functional consequence(s) of IL-12Rbeta2 gene silencing in primary B cell tumors and transformed B cell lines. Purified tumor cells from 41 patients with different chronic B cell lymphoproliferative disorders, representing the counterparts of the major mature human B cell subsets, tested negative for IL-12Rbeta2 gene expression. Hypermethylation of a CpG island in the noncoding exon 1 was associated with silencing of this gene in malignant B cells. Treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine restored IL-12Rbeta2 mRNA expression in primary neoplastic B cells that underwent apoptosis following exposure to human recombinant IL-12 (hrIL-12). hrIL-12 inhibited proliferation and increased the apoptotic rate of IL-12Rbeta2-transfected B cell lines in vitro. Finally, hrIL-12 strongly reduced the tumorigenicity of IL-12Rbeta2-transfected Burkitt lymphoma RAJI cells in SCID-NOD mice through antiproliferative and proapoptotic effects, coupled with neoangiogenesis inhibition related to human IFN-gamma-independent induction of hMig/CXCL9. The IL-12Rbeta2 gene acts as tumor suppressor in chronic B cell malignancies, and IL-12 exerts direct antitumor effects on IL-12Rbeta2-expressing neoplastic B cells.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15173892-10477712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15173892-10532589,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15173892-9916800
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9738
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pubmed:author |
pubmed-author:AiroldiIrmaI,
pubmed-author:AmadoriAlbertoA,
pubmed-author:BanelliBarbaraB,
pubmed-author:CoccoClaudiaC,
pubmed-author:Di CarloEmmaE,
pubmed-author:MoserleLidiaL,
pubmed-author:PezzoloAnnalisaA,
pubmed-author:PistoiaVitoV,
pubmed-author:RomaniMassimoM,
pubmed-author:RossiEdoardoE,
pubmed-author:SorrentinoCarloC
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pubmed:issnType |
Print
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pubmed:volume |
113
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1651-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15173892-Animals,
pubmed-meshheading:15173892-Azacitidine,
pubmed-meshheading:15173892-B-Lymphocytes,
pubmed-meshheading:15173892-Chronic Disease,
pubmed-meshheading:15173892-DNA Modification Methylases,
pubmed-meshheading:15173892-Genes, Tumor Suppressor,
pubmed-meshheading:15173892-Humans,
pubmed-meshheading:15173892-Interleukin-12,
pubmed-meshheading:15173892-Leukemia, B-Cell,
pubmed-meshheading:15173892-Lymphoproliferative Disorders,
pubmed-meshheading:15173892-Mice,
pubmed-meshheading:15173892-Mice, Inbred NOD,
pubmed-meshheading:15173892-Mice, SCID,
pubmed-meshheading:15173892-Palatine Tonsil,
pubmed-meshheading:15173892-Receptors, Interleukin,
pubmed-meshheading:15173892-Receptors, Interleukin-12
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pubmed:year |
2004
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pubmed:articleTitle |
The IL-12Rbeta2 gene functions as a tumor suppressor in human B cell malignancies.
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pubmed:affiliation |
Laboratory of Oncology, G. Gaslini Institute, Genoa, Italy. laboncologia@ospedale-gaslini.ge.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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