PTEN/MMAC1 enhances the growth inhibition by anticancer drugs with downregulation of IGF-II expression in gastric cancer cells.
- Author:
Pyoung Han HWANG
1
;
Sun Young KIM
;
Jung Chang LEE
;
Sun Jun KIM
;
Ho Keun YI
;
Dae Yeol LEE
Author Information
1. Department of Pediatrics, Chonbuk National University Jeonju, Jeonbuk 561-712, Korea. leedy@moak.chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
genes, tumor supprressor;
insulin-like growth factor II;
receptor, IGF type I;
stomach neoplasms
- MeSH:
Antineoplastic Agents/*pharmacology;
Cell Line, Tumor;
Cell Proliferation/drug effects;
*Down-Regulation;
Humans;
Insulin-Like Growth Factor II/*genetics/*metabolism;
PTEN Phosphohydrolase/genetics/*metabolism;
Receptor, IGF Type 1/genetics/metabolism;
Research Support, Non-U.S. Gov't;
Stomach Neoplasms/*genetics/metabolism/*pathology
- From:Experimental & Molecular Medicine
2005;37(5):391-398
- CountryRepublic of Korea
- Language:English
-
Abstract:
PTEN/MMAC1 is a tumor suppressor gene that is mutated in a variety of advanced and metastatic cancers. Its major function is likely to be the phosphatase activity that regulates the phosphotidylinositol (PI)3-kinase/ Akt pathway. On the other hand, IGF system plays an important role in cell proliferation and cell survival via PI3-kinase/Akt and mitogen-activated protein kinase pathways in many cancer cells. To evaluate effect of PTEN on cell growth and IGF system in gastric cancer, human gastric adenocarcinoma cells (SNU-5 & -216) were transfected with human PTEN cDNA. Those PTEN- transfected gastric cancer cells had a lower proliferation rate than the pcDNA3-transfected cells. PTEN overexpression induced a profound decrease in the IGF-II and IGF-IR expression levels, and downregulation of IGF-II expression by PTEN was mediated through the regulation of the IGF-II promoter. In addition, a PI3-kinase inhibitor, LY294002, induced the downregulation of IGF-II expression. The PTEN-overexpressing SUN-5 and -216 cells were more sensitive to death induced by etoposide and adriamycin that induce DNA damage than the pcDNA3-transfected cells. These findings suggest that PTEN suppresses the cell growth through modulation of IGF system and sensitizing cancer cells to cell death by anticancer drugs.
