Tuesday, 12 November 2013

The regulation of mitochondrial DNA copy number in glioblastoma cells

The regulation of mitochondrial DNA copy number in glioblastoma cells


Embryonic stem cells and cancer cells share a number of similarities. Both are highly proliferative (stem cells needing to find a tissue to differentiate at, and cancers are malignant by their nature), glycolytic and have a low copy number of mtDNA. This study compares human neuronal stem cells (hNSCs) and a highly malignant brain cancer called glioblastoma multiforme (GBM). It was shown that hNSCs increase their mtDNA copy number in a cell-specific way during differentiation to a mtDNA "setpoint". When induced to differentiate, GBM fails to match hNSCs expansion in copy number, patterns of gene expression and increased respitatory capacity. However, if mtDNAs are depleted from a GBM and transferred to a mouse, if a tumour manages to form, it is observed that the mtDNA copy number is recovered to in vitro levels, indicating GBM also has an mtDNA setpoint. It is interesting to note that, once mtDNA was depleted from GBM cells and allowed to form a tumour in nude mice, the survival time from largest to smallest was the following: 0.2% (>100 days), 3% (~95 days), 100% (~85 days), 20% (~81 days) and 50% (~78 days), where the percentage indicates the amount of mtDNA remaining in the GBM cells before transfer.


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