|
KMID : 0620920050370050391
|
|
Experimental & Molecular Medicine
2005 Volume.37 No. 5 p.391 ~ p.398
|
|
|
PTEN/MMAC1 enhances the growth inhibition by anticancer drugs with downregulation of IGF-II expression in gastric cancer cells
|
|
Hwang Pyoung-Han
Kim Sun-Young
Lee Jung-Chang
Kim Sun-Jun
Yi Ho-Keun
Lee Dae-Yeol
|
|
|
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 PTENtransfected gastric cancer cells had a lower pro - liferation 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.
|
|
|
KEYWORD
|
|
|
genes, tumor supprressor, insulin-like growth factor II, receptor, IGF type I, stomach neoplasms
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|