Therapeutic potential of antisense oligodeoxynucleotides in downregulating p53 oncogenic mutations in cancers.
Biotechnol Lett
; 33(2): 221-8, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-20882314
ABSTRACT
PURPOSE OF WORK mutation of the p53 gene is the most common genetic alteration in human cancers. Our study proposes to rationally design a p53 antisense oligonucleotide (ASO) repository, which contains a series of ASOs containing single nucleotide differences to discriminate between each mutant and wild type (WT) p53. The Sfold software was used to predict target-accessibility and we designed an initial series of antisense oligonucleotides (ASO) that target the p53 mutants A161T, R175H and R249S. Western-blot analysis indicated that ASOs strongly inhibited the expression of p53 mutants in a panel of human tumor cell lines (SNU-449, SK-BR-3 and PLC/PRF/5) while having little effect on the expression of WT p53 (HepG2 cells). In three cancer lines harboring each of the p53 mutations, mutant-specific ASO treatment led to a dose-dependent inhibition of cell growth, cell viability, colony formation and invasion, and expression of mutant p53-dependent survival proteins. Our preliminary results indicate that a single nucleotide difference in ASOs can discriminate between mutant and WT p53. These observations support the hypothesis that a p53 ASO repository can be a potentially valuable tool to knock down oncogenic mutant p53 and warrant the testing of a p53 ASO repository in in vivo settings.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
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Oligodesoxirribonucleotídeos Antissenso
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Mutação de Sentido Incorreto
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Proteínas Mutantes
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Biotechnol Lett
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Singapura