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Overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1), leads to mitochondrial aberrations in mouse fibroblast NIH/3T3 cells

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Cancer cells undergo uncontrolled proliferation, and aberrantmitochondrial alterations. Tumor necrosis factor receptorassociatedprotein 1 (TRAP1) is a mitochondrial heat shockprotein. TRAP1 mRNA is highly expressed in some cancer celllines and tumor tissues. However, the effects of its overexpressionon mitochondria are unclear. In this study, we assessedmitochondrial changes accompanying TRAP1 overexpression,in a mouse cell line, NIH/3T3. We found that overexpressionof TRAP1 leads to a series of mitochondrial aberrations,including increase in basal ROS levels, and decrease inmitochondrial biogenesis, together with a decrease in peroxisomeproliferator-activated receptor gamma coactivator-1α(PGC-1α) mRNA levels. We also observed increased extracellularsignal-regulated kinase (ERK) phosphorylation, andenhanced proliferation of TRAP1 overexpressing cells. Thisstudy suggests that overexpression of TRAP1 might be a criticallink between mitochondrial disturbances and carcinogenesis.

Abstract

Cancer cells undergo uncontrolled proliferation, and aberrantmitochondrial alterations. Tumor necrosis factor receptorassociatedprotein 1 (TRAP1) is a mitochondrial heat shockprotein. TRAP1 mRNA is highly expressed in some cancer celllines and tumor tissues. However, the effects of its overexpressionon mitochondria are unclear. In this study, we assessedmitochondrial changes accompanying TRAP1 overexpression,in a mouse cell line, NIH/3T3. We found that overexpressionof TRAP1 leads to a series of mitochondrial aberrations,including increase in basal ROS levels, and decrease inmitochondrial biogenesis, together with a decrease in peroxisomeproliferator-activated receptor gamma coactivator-1α(PGC-1α) mRNA levels. We also observed increased extracellularsignal-regulated kinase (ERK) phosphorylation, andenhanced proliferation of TRAP1 overexpressing cells. Thisstudy suggests that overexpression of TRAP1 might be a criticallink between mitochondrial disturbances and carcinogenesis.

참고문헌 (38)

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