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KMID : 0367420040470080884
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Journal of Korean Pediatric Society
2004 Volume.47 No. 8 p.884 ~ p.891
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The Tumor Suppressor Function of PTEN/MMAC1 through the Regulation of IGFs and IGFBPs.
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Yi Ho-Keun
Hwang Dong-Jin
Kim Sun-Young
Lee Dae-Yeol
Hwang Pyoung-Han
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Abstract
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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. (Korean J Pediatr 2004; 47:884-891)
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KEYWORD
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Genes, Tumor suppressor, Insulin-like growth factor I, Insulin-like growth factor II, Insulin-like growth-factor-binding proteins, Phosphatidylinositol 3-kinase, Stomach neoplasms
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