IGF-1 induces expression of zinc-finger protein 143 in colon cancer cells through phosphatidylinositide 3-kinase and reactive oxygen species

• Published in: Experimental & molecular medicine Vol. 42; no. 10; pp. 696 - 702
• Main Authors: Paek, A Rome, Kim, Seok Hyun, Kim, Sun Shin, Kim, Kyung Tae, You, Hye Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2010; Springer Nature B.V; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Antineoplastic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Cisplatin - pharmacology; Colonic Neoplasms - enzymology; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; HCT116 Cells; Humans; Insulin-Like Growth Factor I - pharmacology; Medical Biochemistry; Molecular Medicine; Original; Phosphatidylinositol 3-Kinase - metabolism; Reactive Oxygen Species - metabolism; Signal Transduction; Stem Cells; Trans-Activators - biosynthesis; Trans-Activators - genetics; Xenopus; 생화학; ZNF143 protein, human; 1-phosphatidylinositol 3-kinase; drug resistance, neoplasm; insulin-like growth factor I; reactive oxygen species
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.3858/emm.2010.42.10.068

Expression of zinc-finger protein 143 (ZNF143), a human homolog of the Xenopus transcriptional activator protein Staf, is induced by various DNA-damaging agents including etoposide, doxorubicin, and γ-irradiation. ZNF143 binds to cisplatin-modified DNA, and its levels are increased in cancer cells that are resistant to anticancer drugs, including cisplatin, suggesting that it plays a role in carcinogenesis and cancer cell survival. However, the mechanism of ZNF143 induction in cancer cells remains unclear. Both insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) have been reported to be overexpressed in cancer cells and to be related to anticancer drug resistance, but the identity of the relevant signaling mediators is still being investigated. In the present study, we observed that IGF-1 was able to induce ZNF143 expression in HCT116 human colon cancer cells and that wortmannin, an inhibitor of phosphatidylinositide 3-kinase (PI3-kinase), inhibited this induction, as did diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, and monodansylcardavarine (MDC), a receptor internalization inhibitor. Treatment with MDC decreased the IGF-1-stimulated generation of reactive oxygen species. Taken together, these data suggest that IGF-1 induces ZNF143 expression in cancer cells via PI3-kinase and reactive oxygen species generation during receptor internalization.