The Tumor Suppressor Function of PTEN/MMAC1 through the Regulation of IGFs and IGFBPs / 소아과
Korean Journal of Pediatrics
;
: 884-891, 2004.
Artigo
em Coreano
| WPRIM
| ID: wpr-148791
ABSTRACT
PURPOSE:
PTEN/MMAC1, a novel tumor suppressor gene, is mutated in a variety of advanced and metastatic cancers. It acts as a phosphatase, and thereby, regulates the PI-3 kinase/Akt pathway. In this study, we examined to evaluate the new function of anti-tumor effects of PTEN/MMAC1 through the regulation of the IGFs-IGFBPs in gastric cancer cells.METHODS:
PTEN/MMAC1 was expressed in an adenovirus-mediated gene delivery system and introduced into gastric cancer cells(SNU-484 & SNU-668) in vitro. The effect of cell growth and the expression of IGFs and IGFBPs after Ad/PTEN infection was analyzed by MTT assay, RT-PCR and Western immunoblot.RESULTS:
Ad/PTEN infected cells were inhibited in cell growth compared with moak cells and Ad/ LacZ infected cells. Overexpression of PTEN/MMAC1 induced decrease in expression of IGF-I, -II and IGF-I receptors which are known as growth prompt molecules in a variety of cancers. Of the six IGFBPs, the expressions of IGFBP-4 and IGFBP-6 were decreased in Ad/PTEN infected cells. In contrast, IGFBP-3 expression was markedly increased by up to 3-fold in Ad/PTEN infected cells. Overexpression of PTEN/MMAC1 inhibited the activation of Akt/PKB pathway, but had no effect on the MAPK pathway.CONCLUSION:
These findings suggest that the tumor suppressor function of PTEN/MMAC1 is, at least in part, mediated through the down-regulation of IGF-I abd IGF-II, and up-regulation of IGFBP-3 in gastric cancer cells by the inhibition of PI-3 kinase pathway.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Neoplasias Gástricas
/
Fator de Crescimento Insulin-Like I
/
Fator de Crescimento Insulin-Like II
/
Regulação para Baixo
/
Regulação para Cima
/
Western Blotting
/
Genes Supressores de Tumor
/
Receptor IGF Tipo 1
/
Técnicas de Transferência de Genes
/
Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina
Idioma:
Coreano
Revista:
Korean Journal of Pediatrics
Ano de publicação:
2004
Tipo de documento:
Artigo
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