Selective cell death of p53-insufficient cancer cells is induced by knockdown of the mRNA export molecule GANP.
Apoptosis
; 17(7): 679-90, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22395445
ABSTRACT
Cancer cells often contain p53 abnormalities that impair cell-cycle checkpoint progression and cause resistance to various anti-cancer treatments. DNA damage occurs at actively transcribed genes during G1-phase in yeast cells that have a deficient mRNA export capacity. Here, we show that germinal center-associated nuclear protein (GANP), a homologue of yeast Sac3 that is involved in mRNA export, is indispensable for ensuring the stability of human genomic DNA and that GANP knockdown causes apoptosis and necrosis of p53-insufficient cancer cells. Ganp small interfering RNA (siGanp)-induced DNA damage, accompanied by a decrease in the number of cells in S-phase, caused late apoptosis and necrosis in p53-insufficient cancer cells through both caspase-dependent and -independent mechanisms. siGanp effectively induced DNA damage leading to cell death in p53-insufficient cancer cells in vitro and protect the growth of cancer cells transplanted into immunocompromized mice, suggesting that siGanp has potential as a selective treatment for p53-insufficient cancer cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetiltransferases
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Proteína Supressora de Tumor p53
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Transporte de RNA
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Técnicas de Silenciamento de Genes
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article