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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
1999-4-22
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pubmed:abstractText |
Friend virus-induced erythroleukemia involves two members of the ETS family of transcriptional regulators, both activated via proviral insertion in the corresponding loci. Spi-1/PU.1 is expressed in the disease induced by the original Friend virus SFFV(F-MuLV) complex in adult mice. In contrast, FLI-1 is overexpressed in about 75% of the erythroleukemias induced by the F-MuLV helper virus in newborn mice. To analyse the consequences of the enforced expression of FLI-1 on erythroblast differentiation and proliferation and to compare its activity to that of PU.1/Spi-1, we used a heterologous system of avian primary erythroblasts previously described to study the cooperation between Spi-1/PU.1 and the other molecular alterations observed in SFFV-induced disease. FLI-1 was found: (i) to inhibit the apoptotic cell death program normally activated in erythroblasts following Epo deprivation; (ii) to inhibit the terminal differentiation program induced in these cells in response to Epo and; (iii) to induce their proliferation. However, in contrast to Spi-1/PU.1, the effects of FLI-1 on erythroblast, differentiation and proliferation did not require its cooperation with an abnormally activated form of the EpoR. Enhanced survival of FLI-1 expressing erythroblasts correlated with the upregulation of bcl2 expression. FLI-1 also prevented the rapid downregulation of cyclin D2 and D3 expression normally observed during Epo-induced differentiation and delayed the downregulation of several other genes involved in cell cycle or cell proliferation control. Our results show that overexpression of FLI-1 profoundly deregulates the normal balance between differentiation and proliferation in primary erythroblasts. Thus, the activation of FLI-1 expression observed at the onset of F-MuLV-induced erythroleukemia may provide a proliferative advantage to virus infected cells that would otherwise undergo terminal differentiation or cell death.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D3,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fli1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Protein c-fli-1,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1597-608
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10102630-Amino Acid Sequence,
pubmed-meshheading:10102630-Animals,
pubmed-meshheading:10102630-Apoptosis,
pubmed-meshheading:10102630-Cell Differentiation,
pubmed-meshheading:10102630-Cell Division,
pubmed-meshheading:10102630-Cells, Cultured,
pubmed-meshheading:10102630-Chickens,
pubmed-meshheading:10102630-Cyclin D2,
pubmed-meshheading:10102630-Cyclin D3,
pubmed-meshheading:10102630-Cyclins,
pubmed-meshheading:10102630-DNA, Complementary,
pubmed-meshheading:10102630-DNA-Binding Proteins,
pubmed-meshheading:10102630-Erythroid Precursor Cells,
pubmed-meshheading:10102630-Erythropoiesis,
pubmed-meshheading:10102630-Fibroblasts,
pubmed-meshheading:10102630-Friend murine leukemia virus,
pubmed-meshheading:10102630-Gene Expression Regulation,
pubmed-meshheading:10102630-Genes, bcl-2,
pubmed-meshheading:10102630-Mice,
pubmed-meshheading:10102630-Molecular Sequence Data,
pubmed-meshheading:10102630-Proto-Oncogene Protein c-fli-1,
pubmed-meshheading:10102630-Proto-Oncogene Proteins,
pubmed-meshheading:10102630-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10102630-Receptors, Erythropoietin,
pubmed-meshheading:10102630-Sequence Alignment,
pubmed-meshheading:10102630-Sequence Homology, Amino Acid,
pubmed-meshheading:10102630-Trans-Activators,
pubmed-meshheading:10102630-Transfection
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pubmed:year |
1999
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pubmed:articleTitle |
FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts.
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pubmed:affiliation |
CNRS UMR146, Institut Curie-Section de Recherche, Centre Universitaire, Orsay, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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