Park K.-S.,Cancer Cell and Molecular Biology Branch |
Park K.-S.,Kyung Hee University |
Kim D.-S.,Cancer Cell and Molecular Biology Branch |
Ko C.,Cancer Cell and Molecular Biology Branch |
And 2 more authors.
Frontiers in Bioscience - Elite | Year: 2011
Increased levels of transglutaminase 2 (TGase 2) expression have been reported in many inflammatory diseases, as well as in drug resistant cancer cells. Previous reports have shown that TGase 2 is capable of inducing nuclear factor-kappaB (NF-kappaB) activation via depletion of inhibitor of kappaB (I-kappaB)α through polymerization in the absence of I-kappaBalpha kinase activation. This raises the question of whether increased expression of TGase 2 can extend NF-kappaB activation mediated by a canonical activation pathway. In the TGase 2-inducible EcR23/TG cell line, TGase 2 over-expression resulted in sustained activation of NF-κB in the presence of TNF-alpha, for up to 24 hrs, while in the absence of TGase 2 induction, NF-kappaB activity was restored to basal levels within 6 hrs of TNF-alpha treatment. In mice injected with an adenovirus vector expressing TGase 2, NF-kappaB was constitutively activated for up to 5 days, whereas Adeno/GFP-injected mice exhibited attenuated activation of NF-kappaB in response to TNF-α stress. Thus, the presence of increased levels of TGase 2 may exacerbate NF-κB activation in inflammatory states.
Rome Paek A.,Carcinogenesis Branch |
Kim S.H.,Carcinogenesis Branch |
Kim S.S.,Carcinogenesis Branch |
Kim K.T.,Research Institute National Cancer Center |
You H.J.,Carcinogenesis Branch
Experimental and Molecular Medicine | Year: 2010
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 dedecreased 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.