Mitochondrial Biogenesis Drives Tumor Cell Proliferation

作者：Martinez Outschoorn Ubaldo E^*; Pavlides Stephanos; Sotgia Federica; Lisanti Michael P

来源：American Journal Of Pathology, 2011, 178(5): 1949-1952.

DOI：10.1016/j.ajpath.2011.03.002

Arsenic induces skin cancer and also lung, liver, kidney, prostate, and bladder cancer.(4) Arsenic can dissociate from soil or rocks, and arsenic contamination of the aquifer water supply is a global public health crisis. The study by Lee et al(1) provides new important information on the mechanism(s) by which arsenic induces Bowen's disease, a type of skin carcinoma in situ.
The study by Lee et al(1) demonstrates that arsenic exposure is associated with increased mitochondrial biogenesis (Figure 1), as measured by mitochondrial DNA (mtDNA) copy number. In addition, there is increased expression of peroxisome proliferator-activated receptor gamma, co-activator 1 alpha (PPARGC1A), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM; mtTFA protein), which are crucial genes for mitochondrial biogenesis, compared to normal healthy controls and patients with Bowen's disease without arsenic exposure. Keratinocytes exposed to low-dose arsenic have increased proliferation and expression of the previously stated mitochondrial biogenesis genes at the mRNA and protein levels. Low dose arsenic exposure leads to the up-regulation of mitochondrial oxidative phosphorylation enzyme subunits. Functionally, pharmacological down-regulation of mitochondrial function with oligomycin (a complex V inhibitor of electron transport chain involved in oxidative phosphorylation) abolishes the growth advantage provided by arsenic. Finally, this study shows that genetic down-regulation of mtTFA in keratinocytes leads to abrogation of the growth advantage provided by low dose arsenic.

• 出版日期2011-5