Source:http://linkedlifedata.com/resource/pubmed/id/14744772
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2004-1-27
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| pubmed:abstractText |
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cyclin D homolog, K cyclin, that is thought to promote viral oncogenesis. However, expression of K cyclin in cultured cells not only triggers cell cycle progression but also engages the p53 tumor suppressor pathway, which probably restricts the oncogenic potential of K cyclin. Therefore, to assess the tumorigenic properties of K cyclin in vivo, we transgenically targeted expression of K cyclin to the B and T lymphocyte compartments via the E micro promoter/enhancer. Around 17% of E micro -K cyclin animals develop lymphoma by 9 months of age, and all such lymphomas exhibit loss of p53. A critical role of p53 in suppressing K cyclin-induced lymphomagenesis was confirmed by the greatly accelerated onset of B and T lymphomagenesis in all E micro -K cyclin/p53(-/-) mice. However, absence of p53 did not appear to accelerate K cyclin-induced lymphomagenesis by averting apoptosis: E micro -K cyclin/p53(-/-) end-stage lymphomas contained abundant apoptotic cells, and transgenic E micro -K cyclin/p53(-/-) lymphocytes in vitro were not measurably protected from DNA damage-induced apoptosis compared with E micro -K cyclin/p53(wt) cells. Notably, whereas aneuploidy was frequently evident in pre-lymphomatous tissues, end-stage E micro -K cyclin/p53(-/-) tumors showed a near-diploid DNA content with no aberrant centrosome numbers. Nonetheless, such tumor cells did harbor more restricted genomic alterations, such as single-copy chromosome losses or gains or high-level amplifications. Together, our data support a model in which K cyclin-induced genome instability arises early in the pre-tumorigenic lymphocyte population and that loss of p53 licenses subsequent expansion of tumorigenic clones.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
64
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
581-9
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| pubmed:dateRevised |
2006-5-1
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| pubmed:meshHeading |
pubmed-meshheading:14744772-Animals,
pubmed-meshheading:14744772-Cell Line, Tumor,
pubmed-meshheading:14744772-Crosses, Genetic,
pubmed-meshheading:14744772-Cyclins,
pubmed-meshheading:14744772-DNA Primers,
pubmed-meshheading:14744772-Female,
pubmed-meshheading:14744772-Genes, p53,
pubmed-meshheading:14744772-Genotype,
pubmed-meshheading:14744772-Herpesvirus 8, Human,
pubmed-meshheading:14744772-Kinetics,
pubmed-meshheading:14744772-Lymphangiogenesis,
pubmed-meshheading:14744772-Lymphoma, B-Cell,
pubmed-meshheading:14744772-Male,
pubmed-meshheading:14744772-Mice,
pubmed-meshheading:14744772-Mice, Inbred C57BL,
pubmed-meshheading:14744772-Mice, Inbred CBA,
pubmed-meshheading:14744772-Mice, Knockout,
pubmed-meshheading:14744772-Mice, Transgenic,
pubmed-meshheading:14744772-Plasmids,
pubmed-meshheading:14744772-Polymerase Chain Reaction,
pubmed-meshheading:14744772-T-Lymphocytes,
pubmed-meshheading:14744772-Tumor Suppressor Protein p53,
pubmed-meshheading:14744772-Viral Proteins
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| pubmed:year |
2004
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| pubmed:articleTitle |
The role of p53 in suppression of KSHV cyclin-induced lymphomagenesis.
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| pubmed:affiliation |
Comprehensive Cancer Center and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, USA.
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| pubmed:publicationType |
Journal Article
|