The anti-tumor mechanisms of p53 through the regulation of expression and glycosylation of insulin-like growth factor binding protein-3 / 소아과
Korean Journal of Pediatrics
; : 431-438, 2006.
Article
em Ko
| WPRIM
| ID: wpr-210312
Biblioteca responsável:
WPRO
ABSTRACT
PURPOSE: Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. METHODS: The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. RESULTS: Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. CONCLUSION: From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.
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Índice:
WPRIM
Assunto principal:
Glicosilação
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Neoplasias da Mama
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Terapia Genética
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Adenoviridae
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Processamento de Proteína Pós-Traducional
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Western Blotting
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Genes Supressores de Tumor
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Apoptose
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Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina
Limite:
Humans
Idioma:
Ko
Revista:
Korean Journal of Pediatrics
Ano de publicação:
2006
Tipo de documento:
Article