The Tumor Suppressor Function of PTEN/MMAC1 through the Regulation of IGFs and IGFBPs.
- Author:
Ho Keun YI
1
;
Dong Jin HWANG
;
Sun Young KIM
;
Dae Yeol LEE
;
Pyoung Han HWANG
Author Information
1. Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju, Korea. hwaph@chonbuk.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Genes;
Tumor suppressor;
Insulin-like growth factor I;
Insulin-like growth factor II;
Insulin-like growth-factor-binding proteins;
Phosphatidylinositol 3-kinase;
Stomach neoplasms
- MeSH:
Blotting, Western;
Down-Regulation;
Gene Transfer Techniques;
Genes, Tumor Suppressor;
Insulin-Like Growth Factor Binding Protein 3;
Insulin-Like Growth Factor Binding Protein 4;
Insulin-Like Growth Factor Binding Protein 6;
Insulin-Like Growth Factor Binding Proteins*;
Insulin-Like Growth Factor I;
Insulin-Like Growth Factor II;
Phosphatidylinositol 3-Kinase;
Phosphatidylinositol 3-Kinases;
Receptor, IGF Type 1;
Stomach Neoplasms;
Up-Regulation
- From:Korean Journal of Pediatrics
2004;47(8):884-891
- CountryRepublic of Korea
- Language:Korean
-
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.
