IGF-1 induces expression of zinc-finger protein 143 in colon cancer cells through phosphatidylinositide 3-kinase and reactive oxygen species.
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 gamma-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.
Paek
A Rome
AR
Carcinogenesis Branch, Division of Cancer Biology, Research Institute National Cancer Center, Goyang 410-769, Korea.
Kim
Seok Hyun
SH
Kim
Sun Shin
SS
Kim
Kyung Tae
KT
You
Hye Jin
HJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D015534:Trans-Activators; C114253:ZNF143 protein, human; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D002945:Cisplatin