All issues > Volume 47(8); 2004

Original Article

Korean J Pediatr. 2004;47(8):884-891. Published online August 15, 2004.

The Tumor Suppressor Function of PTEN/MMAC1 through the Regulation of IGFs and IGFBPs

Ho Keun HK Yi¹, Dong Jin DJ Hwang², Sun Young SY Kim², Dae Yeol DY Lee², Pyoung Han PH Hwang²

¹Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju, Korea
²Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju, Korea

Correspondence Pyoung Han PH Hwang ,Email: hwaph@chonbuk.ac.kr

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.

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