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Titolo:
Germ-line deletion of p53 reveals a multistage tumor progression in spi-1/PU.1 transgenic proerythroblasts
Autore:
Le Scolan, E; Wendling, F; Barnache, S; Denis, N; Tulliez, M; Vainchenker, W; Moreau-Gachelin, F;
Indirizzi:
Inst Curie, INSERM, U528, F-75005 Paris, France Inst Curie Paris France F-75005 rie, INSERM, U528, F-75005 Paris, France Inst Gustave Roussy, INSERM, U362, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France Hop Cochin, Lab Anat, F-75014 Paris, France Hop Cochin Paris France F-75014 Cochin, Lab Anat, F-75014 Paris, France
Titolo Testata:
ONCOGENE
fascicolo: 39, volume: 20, anno: 2001,
pagine: 5484 - 5492
SICI:
0950-9232(20010906)20:39<5484:GDOPRA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILD-TYPE P53; VIRUS-INDUCED ERYTHROLEUKEMIA; TRANSCRIPTION FACTOR PU.1; LONG TERMINAL REPEAT; DNA-BINDING PROTEIN; FRIEND-VIRUS; ERYTHROPOIETIN RECEPTOR; CELL-DIFFERENTIATION; HEMATOPOIETIC-CELLS; MICE DEFICIENT;
Keywords:
erythroleukemia; Spi-1/PU.1; p53; p2l(Cip1/Waf1); transgenic mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Moreau-Gachelin, F Inst Curie, INSERM, U528, 26 Rue Ulm, F-75005 Paris, France Inst Curie 26 Rue Ulm Paris France F-75005 ris, France
Citazione:
E. Le Scolan et al., "Germ-line deletion of p53 reveals a multistage tumor progression in spi-1/PU.1 transgenic proerythroblasts", ONCOGENE, 20(39), 2001, pp. 5484-5492

Abstract

Activation of the spi-1/PU.1 proto-oneogene and loss of p53 function are genetic alterations associated with the emergence of Friend malignant erythroleukemic cells. To address the role of p53 during erythroleukemogenesis, spi-1 transgenic mice (spi-1-Tg) which develop erythroleukemia were bred with p53-deficient mice. Three classes of spi-1 transgenic mice differing in their p53 functional status (p53(+/+), p53(+/-) and p53(-/-)) were generated. These mice developed a unique pattern of erythroleukemia. In wild-type p53 spi-1-Tg mice, none of the primary erythroleukemic spleen cells displayedautonomous growth in vitro and in vivo. In contrast, in p53(+/-) spi-1-Tg mice, erythroleukemic cells gave rise to growth factor-independent cell lines and generated tumors in vivo. Malignancy was associated with loss of thewild-type p53 allele. The p53(-/-) spi-1-Tg mice developed erythroleukemiawith a total incidence and a reduced latency compared to the two other genotypes. Unexpectedly, 50% of p53(-/-) spi-1-Tg erythroleukemic spleens generated cell lines that were strictly dependent upon erythropoietin (Epo) forproliferation, whereas the remainder proliferated independently of cytokines. Moreover, only 70% of these spleen cells were tumorigenic. These findings indicate that p53 germ-line deletion did not confer malignancy to spi-1-transgenic proerythroblasts. Moreover Epo independence and tumorigenicity appear as separable phenotypic characteristics revealing that the spi-1-Tg proerythroblasts progress towards malignancy through multiple oncogenic events.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/10/20 alle ore 23:38:05