PTEN/MMAC1 enhances the growth inhibition by anticancer drugs with downregulation of IGF-II expression in gastric cancer cells

• Published in: Experimental & molecular medicine Vol. 37; no. 5; pp. 391 - 398
• Main Authors: Hwang, Pyoung Han, Kim, Sun Young, Lee, Jung Chang, Kim, Sun Jun, Yi, Ho Keun, Lee, Dae Yeol
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 31.10.2005
• Subjects: Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Down-Regulation; Humans; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/emm.2005.49

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.