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.