Establishment of cancer cell models derived from human iPS cells based on mitochondrial complex II deficiency
Sugako Oka1, Michio Hayashi 2, Mutsuo Sekiguchi 1 1Frontier Research Center, 2Section of Biochemistry, Fukuoka Dental College
Oxidative stress plays a pivotal role in the differentiation and proliferation of cells and programmed cell death, and may cause oncogenesis and aging. Studies of the role of oxidative stress in oncogenesis have mainly employed human cancer cell lines. However, such cancer cell lines show characteristics that differ from those of the original tissue and exhibit resistance to oxidative stress by harboring various mutations. Therefore, cancer cell models that accurately reflect the influence of oxidative stress are required. The SDHC gene encoding mitochondrial succinate dehydrogenase complex subunit C has been identified as causing familial paragangliomas, and programmed cell death accompanying increased endogenous oxidative stress was observed in Tet- mev-1 mice overexpressing mutant SDHC (I69E) protein. In the present study, we report the construction of human iPS cell lines exhibiting a change in endogenous ROS production due to regulation of the expression of mutant SDHC or mitochondrial-targeted human catalase, or both, under the Tet-ProteoTuner system. Using these cell lines, we have established cancer cell models derived from human iPS cells and clarified the endogenous role of ROS in oncogenesis.
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