| The Tumor Suppressor Function of PTEN/MMAC1 through the Regulation of IGFs and IGFBPs |
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Ho Keun Yi1, Dong Jin Hwang2, Sun Young Kim2, Dae Yeol Lee2, Pyoung Han Hwang2 |
1Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju, Korea
2Department of Pediatrics, School of Medicine, Chonbuk National University, Jeonju, Korea |
| 종양 세포주에서 IGFs와 IGFBPs의 제어를 통한 PTEN/MMAC1의 암억제 기능 |
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이호근1, 황동진2, 김선영2, 이대열2, 황평한2 |
1전북대학교 치과대학 생화학교실
2전북대학교 의과대학 소아과학교실 |
Correspondence:
Pyoung Han Hwang, Email: hwaph@chonbuk.ac.kr
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| 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. |
| Key Words:
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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