Rit42 is an Energy-Governor Molecule Which Prevents Over-Synthesis of ATP.

摘要

RTP/DRG/Cap43/Rit42 gene is highly expressed in normal prostate cells, but is weakly expressed in prostate cancer cells. The inducible expression by hypoxia is low in normal prostate cells, but is significantly increased in prostate cancer cells. In this study, we report that radiation and various anti-androgens including hydroflutamide, Casodex, and cyproterone acetate greatly induce RTP/DRG/Cap43/Rit42 mRNA expression in a time- and dose- dependent manner. The effect is observed in both human breast tumor (MCF-7) and in prostate cancer cells (LNCaP), but not in cultured normal prostate epithelial cells. The in vitro growth rate of MCF-7 cells was markedly reduced after stable transfection of the Rit42 gene using a tetracycline-inducible system. A yeast two-hybrid study demonstrated that RTP/DRG/Cap43/Rit42 protein binds with cytochrome C oxidase VIb. In this work, RTP/DRG/Cap43/Rit42 gene expression was found to be induced by hypoxia, implying that its association with cytochrome C oxidases may play an important role in regulation of synthesis and consumption of ATP in tumors. Involvement of this gene in the control of cell growth and metabolism, as well as the high inducibility of the gene in tumor cells by hypoxia, radiation, or anti-androgens suggest that RTP/DRG/Cap43/Rit42 might be a novel stress response protein.