Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice
| ISSN: | 0027-8424 |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98deae1c1c7caa45ae3e4de0d563dbca https://pubmed.ncbi.nlm.nih.gov/7937975 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....98deae1c1c7caa45ae3e4de0d563dbca |
| Autor: | Tula Saison-Behmoaras, C. Chavany, Claude Hélène, G Goubin, I. Duroux, G Schwab, J Lebeau |
| Rok vydání: | 1994 |
| Předmět: |
Male
Mutant Molecular Sequence Data Mice Nude Biology Polymerase Chain Reaction Proto-Oncogene Proteins p21(ras) Mice Animals Humans Point Mutation Breast Cyanoacrylates RNA Messenger Messenger RNA Multidisciplinary Base Sequence Cell growth Oligonucleotide Point mutation Translation (biology) Exons Oligonucleotides Antisense Molecular biology Cell Transformation Neoplastic Genes ras Urinary Bladder Neoplasms Tumor progression Mutagenesis Site-Directed Female Adsorption Cell Division Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 91(22) |
| ISSN: | 0027-8424 |
| Popis: | Ras oncogenes owe their transforming properties to single point mutations in the sequence coding for the active site of the p21 protein. These mutations lead to changes in cellular proliferation and induce tumorigenic properties. Point mutations represent a well-defined target for antisense oligonucleotides that can specifically suppress the translation of the targeted mutant mRNA. We show that the stability and cellular disponibility of antisense oligonucleotides can be markedly improved by adsorption to polyalkylcyanoacrylate nanoparticles. Nanoparticle-adsorbed antisense oligonucleotides directed to a point mutation (G-->U) in codon 12 of the Ha-ras mRNA selectively inhibited the proliferation of cells expressing the point-mutated Ha-ras gene at a concentration 100 times lower than free oligonucleotides. In addition they markedly inhibited Ha-ras-dependent tumor growth in nude mice after subcutaneous injection. These experiments show that inhibition of ras oncogenes by antisense oligonucleotides can block tumor development even though ras oncogenic activation might be an early event in tumor progression. |
| Databáze: | OpenAIRE |
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