Linked Life Data

18071306

Source:http://linkedlifedata.com/resource/pubmed/id/18071306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2008-5-22
pubmed:abstractText
Adult T-cell leukemia (ATL) is a mature CD4+ T-cell malignancy etiologically associated with human T-cell leukemia virus type 1 (HTLV-1). Primary ATL cells frequently express CCR4 at high levels. Since HTLV-1 Tax does not induce CCR4 expression, transcription factor(s) constitutively active in ATL may be responsible for its strong expression. We identified an activator protein-1 (AP-1) site in the CCR4 promoter as the major positive regulatory element in ATL cells. Among the AP-1 family members, Fra-2, JunB and JunD are highly expressed in fresh primary ATL cells. Consistently, the Fra-2/JunB and Fra-2/JunD heterodimers strongly activated the CCR4 promoter in Jurkat cells. Furthermore, Fra-2 small interfering RNA (siRNA) or JunD siRNA, but not JunB siRNA, effectively reduced CCR4 expression and cell growth in ATL cells. Conversely, Fra-2 or JunD overexpression promoted cell growth in Jurkat cells. We identified 49 genes, including c-Myb, BCL-6 and MDM2, which were downregulated by Fra-2 siRNA in ATL cells. c-Myb, BCL-6 and MDM2 were also downregulated by JunD siRNA. As Fra-2, these proto-oncogenes were highly expressed in primary ATL cells but not in normal CD4+ T cells. Collectively, aberrantly expressed Fra-2 in association with JunD may play a major role in CCR4 expression and oncogenesis in ATL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3221-32
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18071306-Binding Sites, pubmed-meshheading:18071306-Cell Culture Techniques, pubmed-meshheading:18071306-Cell Line, Tumor, pubmed-meshheading:18071306-Cell Proliferation, pubmed-meshheading:18071306-Fos-Related Antigen-2, pubmed-meshheading:18071306-Gene Expression Profiling, pubmed-meshheading:18071306-Gene Expression Regulation, Leukemic, pubmed-meshheading:18071306-Humans, pubmed-meshheading:18071306-Jurkat Cells, pubmed-meshheading:18071306-Leukemia-Lymphoma, Adult T-Cell, pubmed-meshheading:18071306-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18071306-Promoter Regions, Genetic, pubmed-meshheading:18071306-Protein Binding, pubmed-meshheading:18071306-Proto-Oncogene Proteins c-jun, pubmed-meshheading:18071306-RNA, Small Interfering, pubmed-meshheading:18071306-Receptors, CCR4
pubmed:year
2008
pubmed:articleTitle
Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia.
pubmed:affiliation
Department of Microbiology, Kinki University School of Medicine, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't