The involvement of reactive oxygen species derived from NADPH oxidase-1 activation on the constitutive tyrosine auto-phosphorylation of RET proteins

S. Qiao, K. Fan, T. Iwashita, M. Ichihara, M. Yoshino, M. Takahashi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)427-434
Number of pages8
JournalFree Radical Research
Volume48
Issue number4
DOIs
Publication statusPublished - 04-2014

All Science Journal Classification (ASJC) codes

  • Biochemistry

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