Cyclin D1 antisense oligonucleotide inhibits cell growth stimulated by epidermal growth factor and induces apoptosis of gastric cancer cells.
Jpn J Cancer Res
; 92(10): 1102-9, 2001 Oct.
Article
en En
| MEDLINE
| ID: mdl-11676861
ABSTRACT
The cyclin D1 protein is one of the cell cycle regulators required for cell cycle progression through G1 phase to S phase. The cyclin D1-cyclin-dependent kinase (CDK) system is thought to control the cell cycle through mediating extracellular signals from mitogens, such as epidermal growth factor (EGF). In this study, we attempted to examine the therapeutic effect of cyclin D1 antisense oligonucleotides (AS/D1) on cell proliferation and apoptosis of the gastric cancer cell line MKN-74, in the presence and absence of EGF-stimulation. Evaluation of cell survival and DNA synthesis revealed that enhanced cell growth following EGF-stimulation was completely inhibited by a 24 h pre-incubation with 100 nM AD/D1. This inhibition was down to 19.3% compared with maximal DNA synthesis after stimulation with 3 nM EGF alone. Western blotting demonstrated that while EGF-stimulation led to cyclin D1 over-expression, AS/D1 inhibited cyclin D1 protein expression. We also demonstrated the induction of apoptosis in MKN-74 cells by AS/D1. In conclusion, EGF-stimulated MKN-74 cell proliferation was inhibited by AS/D1, which could overcome EGF-induced cyclin D1 over-expression. AS/D1 also affected cell survival by inducing apoptosis through cell cycle arrest following cyclin D1 depletion. Thus, AS/D1 may be a candidate for use as a novel cancer therapy specifically targeted against the over-expression of cyclin D1 enhanced by EGF in malignant cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Oligonucleótidos Antisentido
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Apoptosis
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Ciclina D1
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Factor de Crecimiento Epidérmico
Límite:
Humans
Idioma:
En
Revista:
Jpn J Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2001
Tipo del documento:
Article