Replicating parvoviruses that target colon cancer cells.

Détails

ID Serval
serval:BIB_28507
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Replicating parvoviruses that target colon cancer cells.
Périodique
Journal of Virology
Auteur⸱e⸱s
Malerba M., Daeffler L., Rommelaere J., Iggo R.D.
ISSN
0022-538X
Statut éditorial
Publié
Date de publication
2003
Volume
77
Numéro
12
Pages
6683-6691
Langue
anglais
Notes
Publication types: Evaluation Studies ; Journal Article
Résumé
The wnt signaling pathway is constitutively activated in colon tumors by mutations in the adenomatous polyposis coli and beta-catenin genes. We have modified the minute virus of mice (MVM) P4 promoter to make it responsive to wnt signaling by inserting binding sites for the heterodimeric beta-catenin/Tcf transcription factor. In luciferase assays we can see up to 20-fold selectivity of Tcf mutant P4 promoters for cells with activated wnt signaling. Hybrid MVM/H-1 viruses containing Tcf mutant promoters were tested for NS1 expression, viral DNA replication, virus replication, and cytopathic effect on colon, lung, kidney, and cervical cancer cell lines. Activation of the wnt pathway by expression of Delta N-beta-catenin increased NS1 expression and viral burst size in 293T and H1299 lung cancer cells, showing that the Tcf mutant P4 promoter can respond to wnt signals in the context of the virus. Compared to the parental virus, the burst size of the Tcf mutant viruses was reduced at least 1,000-fold in H1299, 293T, NB324K, and HeLa cells, which have inactive wnt signaling pathways. The burst size and cytopathic effect of the Tcf viruses was near wild-type levels in SW480 and Isreco1 colon cancer cell lines, which have high Tcf activity. The high specificity of these viruses should permit the development of H-1 virus-based vectors which combine high safety and greater efficacy in cancer therapy.
Mots-clé
Adenomatous Polyposis Coli/genetics, Adenomatous Polyposis Coli/virology, Animals, Binding Sites, Colonic Neoplasms/genetics, Colonic Neoplasms/virology, Cytoskeletal Proteins/genetics, Cytoskeletal Proteins/metabolism, Gene Targeting/methods, Genetic Vectors, Humans, Mice, Minute virus of mice/genetics, Minute virus of mice/physiology, Mutation, Parvovirus/genetics, Parvovirus/pathogenicity, Promoter Regions, Genetic, Proto-Oncogene Proteins/metabolism, Signal Transduction, Trans-Activators/genetics, Trans-Activators/metabolism, Transcription Factors/genetics, Transcription Factors/metabolism, Tumor Cells, Cultured, Virus Replication, Wnt Proteins, Zebrafish Proteins, beta Catenin
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 12:25
Dernière modification de la notice
20/08/2019 13:07
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