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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-10-15
pubmed:abstractText
HCV chronic infection leads to liver diseases and also to a wide range of extrahepatic disorders including benign, but pre-lymphomatous forms (mixed cryoglobulinemia) to frank hematological neoplasia (non-Hodgkin's lymphoma). Recent data showed the involvement of p53 superfamily members in the pathogenesis of different lymphatic malignancies. In fact, tymomas and a subset of non-Hodgkin's lymphomas (NHLs) express high levels of p63. Thus, we analyzed whether alterations in p53 superfamily gene expression are observable in B lymphocytes isolated from HCV-infected patients with and without lymphoproliferative disorders. We showed, by real-time PCR, a significant induction of DNp63 mRNAs in B lymphocytes obtained from HCV-positive low grade non-Hodgkin's lymphoma patients. Since our current understanding of HCV proteins emphasizes the ability of the HCV core protein to deregulate the expression and activity of p53-related proteins, we established different B lymphocyte cell lines (Wil2-ns, Daudi and Ramos) stably expressing HCV core protein, in order to investigate the possible involvement of the viral protein in the upregulation of DNp63 in B lymphocytes. The analysis of p63 family transcripts showed no transcriptional changes for the p63 TA isoforms, whereas an increase (>5 times) of DNp63 mRNA occurred. In all cell lines, this abnormal expression was associated with a significant increase of cell proliferation that was specifically inhibited by silencing DNp63 mRNA. These findings suggest a pathogenetic role of the HCV core in HCV-related lymphomagenesis, through the induction of DNp63's pro-proliferative effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1878-3562
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S72-5
pubmed:dateRevised
2009-5-20
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hepatitis C virus core protein enhances B lymphocyte proliferation.
pubmed:affiliation
Laboratory of Molecular Virology and Oncology, Fondazione A. Cesalpino, University of Rome La Sapienza, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't