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Titolo:
Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1
Autore:
Farassati, F; Yang, AD; Lee, PWK;
Indirizzi:
Univ Calgary, Hlth Sci Ctr, Canc Biol Res Grp, Calgary, AB T2N 4N1, CanadaUniv Calgary Calgary AB Canada T2N 4N1 s Grp, Calgary, AB T2N 4N1, Canada Univ Calgary, Hlth Sci Ctr, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada Univ Calgary Calgary AB Canada T2N 4N1 t Dis, Calgary, AB T2N 4N1, Canada
Titolo Testata:
NATURE CELL BIOLOGY
fascicolo: 8, volume: 3, anno: 2001,
pagine: 745 - 750
SICI:
1465-7392(200108)3:8<745:OIRSPD>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; BRAIN-TUMORS; MUTANT G207; CANCER; TRANSFORMATION; INHIBITOR; REOVIRUS; THERAPY; GLIOMA; PKR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Lee, PWK Univ Calgary, Hlth Sci Ctr, Canc Biol Res Grp, Calgary, AB T2N 4N1, Canada Univ Calgary Calgary AB Canada T2N 4N1 lgary, AB T2N 4N1, Canada
Citazione:
F. Farassati et al., "Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1", NAT CELL BI, 3(8), 2001, pp. 745-750

Abstract

The importance of herpes simplex viruses (HSV) as human pathogens and the emerging prospect of using mutant derivatives of HSV-1 as potential anti-cancer therapeutics have necessitated a thorough investigation into the molecular basis of host-cell permissiveness to HSV. Here we show that NIH-3T3 cells transformed with the oncogenes v-erbB, activated sos or activated ras become significantly more permissive to HSV-1. Inhibitors of the Ras signalling pathway, such as farnesyl transferase inhibitor 1 and PD98069, effectively suppressed HSV-1 infection of ras-transformed cells. Enhanced permissiveness of the transformed cells was linked to the inhibition of virus-induced activation (phosphorylation) of the double-stranded RNA-activated proteinkinase (PKR), thereby allowing viral transcripts to be translated in thesecells. An HSV-1-derived oncolytic mutant, R3616, was also found to infect preferentially both transformed cells and PKR-/- (but not PKR+/+) mouse embryo fibroblasts. These observations suggest that HSV-1 specifically targetscells with an activated Ras signalling pathway, and have important ramifications in the use of engineered HSV in cancer therapy, the development of strategies against HSV infections, and the controversial role of HSV in human cancers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 20:01:10