Aberrant cell proliferation by enhanced mitochondrial biogenesis via mtTFA in arsenical skin cancers

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題名:	Aberrant cell proliferation by enhanced mitochondrial biogenesis via mtTFA in arsenical skin cancers
作者:	Chih-Hung Lee;Shi-Bei Wu;Chien-Hui Hong;Wei-Ting Liao;Ching-Ying Wu;Gwo-Shing Chen;Yau-Huei Wei;Hsin-Su Yu
貢獻者:	醫學系
日期:	2011-05-01
上傳時間:	2012-02-14 15:01:31 (UTC+8)
摘要:	Arsenic-induced Bowen's disease (As-BD), a cutaneous carcinoma in situ, is thought to arise from gene mutation and uncontrolled proliferation. However, how mitochondria regulate the arsenic-induced cell proliferation remains unclear. The aim of this study was to clarify whether arsenic interfered with mitochondrial biogenesis and function, leading to aberrant cell proliferation in As-BD. Skin biopsy samples from patients with As-BD and controls were stained for cytochrome c oxidase (Complex IV), measured for mitochondrial DNA (mtDNA) copy number and the expression levels of mitochondrial biogenesis–related genes, including peroxisome proliferator–activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (mtTFA). The results showed that expression of cytochrome c oxidase, mtTFA, NRF-1, and PGC-1α was increased in As-BD compared with in healthy subjects. Treatment of primary keratinocytes with arsenic at concentrations lower than 1.0 μmol/L induced cell proliferation, along with enhanced mitochondrial biogenesis. Furthermore, we observed that the mitochondrial oxygen consumption rate and intracellular ATP level were increased in arsenic-treated keratinocytes. Blocking of mitochondrial function by oligomycin A (Complex V inhibitor) or knockdown of mtTFA by RNA interference abrogated arsenic-induced cell proliferation without affecting cyclin D1 expression. We concluded that mtTFA up-regulation, augmented mitochondrial biogenesis, and enhanced mitochondrial functions may contribute to arsenic-induced cell proliferation. Targeting mitochondrial biogenesis may help treat arsenical cancers at the stage of cell proliferation.
關聯:	American Journal of Pathology, 178(5), 2066-2076. https://doi.org/10.1016/j.ajpath.2011.01.056
顯示於類別:	[醫學系] 期刊論文

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