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Titolo:
EXPRESSION OF WILD-TYPE AND MUTANT SIMIAN-VIRUS-40 LARGE TUMOR-ANTIGENS IN VILLUS-ASSOCIATED ENTEROCYTES OF TRANSGENIC MICE
Autore:
KIM SH; ROTH KA; COOPERSMITH CM; PIPAS JM; GORDON JI;
Indirizzi:
WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL ST LOUIS MO 63110 WASHINGTON UNIV,SCH MED,DEPT SURG ST LOUIS MO 63110 WASHINGTON UNIV,SCH MED,DEPT PATHOL ST LOUIS MO 63110 UNIV PITTSBURGH,DEPT BIOL SCI PITTSBURGH PA 15260
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 15, volume: 91, anno: 1994,
pagine: 6914 - 6918
SICI:
0027-8424(1994)91:15<6914:EOWAMS>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
LARGE T-ANTIGEN; CELLULAR-DIFFERENTIATION; GUT EPITHELIUM; P53 BINDING; MOUSE; GENE; TRANSFORMATION; PROTEIN; POPULATIONS; REQUIREMENT;
Keywords:
CELL CYCLE REGULATION; [VAL(12)]KRAS; INTESTINAL NEOPLASIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
19
Recensione:
Indirizzi per estratti:
Citazione:
S.H. Kim et al., "EXPRESSION OF WILD-TYPE AND MUTANT SIMIAN-VIRUS-40 LARGE TUMOR-ANTIGENS IN VILLUS-ASSOCIATED ENTEROCYTES OF TRANSGENIC MICE", Proceedings of the National Academy of Sciences of the United Statesof America, 91(15), 1994, pp. 6914-6918

Abstract

The four principal gut epithelial cell lineages undergo continuous and rapid renewal during a geographically well-organized migration alongthe crypt-to-villus axis. The molecules that regulate their proliferation and differentiation programs are largely unknown. The large tumorantigen (TAg) of wild-type (wt) simian virus 40 (SV40) and its mutantderivatives represent tools for describing the contributions of regulators of the cell cycle to the proliferative state of each lineage. Expression of SV40 TAgwt in postmitotic, villus-associated enterocytes of transgenic mice causes them to reenter the cell cycle without an apparent effect on their state of differentiation. When human ERAS with aVal-12 substitution ([Val(12)]KRAS) is coexpressed with SV40 TAgwt invillus enterocytes of bitransgenic animals, the two oncoproteins cooperate to produce dedifferentiation (dysplasia). SV40 mutant dl1137 expresses a TAg that is unable to complex with p53 but retains N-terminaltransforming functions, including the ability to complex pRB, p107, and p300. When SV40 TAgdl1137 is expressed in villus enterocytes, they reenter into the cell cycle. However, coexpression of SV40 TAgdl1137 and [Val(12)]KRAS does not produce dysplastic changes. Thus, the N-terminal 121 residues of TAg are sufficient to perturb the proliferative state of the enterocyte but not to produce detectable changes in the state of differentiation when coexpressed with [Val(12)]KRAS.

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Documento generato il 12/07/20 alle ore 06:37:00