TY - JOUR
T1 - The involvement of reactive oxygen species derived from NADPH oxidase-1 activation on the constitutive tyrosine auto-phosphorylation of RET proteins
AU - Qiao, S.
AU - Fan, K.
AU - Iwashita, T.
AU - Ichihara, M.
AU - Yoshino, M.
AU - Takahashi, M.
N1 - Funding Information:
The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper. This work was supported in part by Chubu University Grant A (25IM20A, S. Qiao).
PY - 2014/4
Y1 - 2014/4
N2 - Reactive oxygen species (ROS) play a key role in neoplastic growth and tumor invasion is supported by various experimental data. In this study, we analyzed the participation of ROS in the RET tyrosine auto-phosphorylation. The NIH3T3 cell lines transfected with cRET, MEN2A, and MEN2B individually (designated NIH3T3cRET, NIH3T3 RET-MEN2A, and NIH3T3RET-MEN2B) showed the elevated levels of intracellular ROS, and concomitantly increased Rac1 expression, as well as down-regulation of Mn SOD and Cu/Zn SOD in comparison with the parental cell line expressing RET. H2O2 enhanced the constitutive tyrosine auto-phosphorylation of RET-MEN2A and RET-MEN2B proteins, and this increase was attenuated by treatment with the NOX inhibitor diphenyliodonium (DPI) or catalase. We also showed that DPI inhibited dimerization of RET-MEN2A. Elevated ROS derived from NOX1 activation and downregulation of SOD in NIH3T3RET-MEN2A and NIH3T3RET-MEN 2B cells may be involved in RET constitutive tyrosine auto-phosphorylation, and scavengers of ROS such as catalase and blocking NOX1 are useful for targeting RET tyrosine kinase activation in cancer.
AB - Reactive oxygen species (ROS) play a key role in neoplastic growth and tumor invasion is supported by various experimental data. In this study, we analyzed the participation of ROS in the RET tyrosine auto-phosphorylation. The NIH3T3 cell lines transfected with cRET, MEN2A, and MEN2B individually (designated NIH3T3cRET, NIH3T3 RET-MEN2A, and NIH3T3RET-MEN2B) showed the elevated levels of intracellular ROS, and concomitantly increased Rac1 expression, as well as down-regulation of Mn SOD and Cu/Zn SOD in comparison with the parental cell line expressing RET. H2O2 enhanced the constitutive tyrosine auto-phosphorylation of RET-MEN2A and RET-MEN2B proteins, and this increase was attenuated by treatment with the NOX inhibitor diphenyliodonium (DPI) or catalase. We also showed that DPI inhibited dimerization of RET-MEN2A. Elevated ROS derived from NOX1 activation and downregulation of SOD in NIH3T3RET-MEN2A and NIH3T3RET-MEN 2B cells may be involved in RET constitutive tyrosine auto-phosphorylation, and scavengers of ROS such as catalase and blocking NOX1 are useful for targeting RET tyrosine kinase activation in cancer.
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U2 - 10.3109/10715762.2014.884278
DO - 10.3109/10715762.2014.884278
M3 - Article
C2 - 24437351
AN - SCOPUS:84895751680
SN - 1071-5762
VL - 48
SP - 427
EP - 434
JO - Free Radical Research
JF - Free Radical Research
IS - 4
ER -
