An international team of researchers finds that the resistance of some cancers to the cell-killing effects of radiation therapy may be due to abnormalities in the mitochondria - the cellular structures responsible for generating energy. Their findings are published in the Nov. 25 issue of Developmental Cell.Maxim Frolov, associate professor of biochemistry and molecular genetics at the University of Illinois at Chicago, and colleagues investigated the effects of a mutation in a gene called E2F, which controls other genes responsible for initiating programmed cell death, a normal function in most cells.
Cells undergo programmed cell death -- or apoptosis -- when they are no longer needed, as a normal part of aging, or in response to environmental factors like radiation that damage cellular DNA. When Frolov and colleagues exposed fruit flies carrying a mutant E2F gene to radiation, genes that initiate apoptosis were activated, but the flies did not die. "Something else was preventing the flies from dying, even though the genes needed to undergo cell death were turned on," Frolov said.
A closer look within the cells of the flies revealed that their mitochondria were misshapen and produced less energy than normal mitochondria. Flies with the most severely deranged mitochondria were the most resistant to radiation-induced cell death. The observation in fruit flies suggested a previously unknown role for the E2F transcription factor -- the protein encoded by E2F that regulates expression of other genes -- in mitochondrial function. "It seems their mitochondria were also affected by the E2F mutation and were not functioning at full strength," said Frolov. "You need properly functioning mitochondria to carry out programmed cell death." Turning to human cells, the researchers found the same effects: those that lacked the E2F gene were resistant to the effects of radiation. Frolov said the similarity in the findings shows that basic cellular functions do not change much across the vast evolutionary distance between fruit flies and humans.