Cancer-Killing Gene Could Help Elephants Avoid Tumors
My research team at the University of Utah has shown that an extra copy of an important tumor suppressor gene could explain how elephants manage to overcome the cancer risk inherent to their large body size.
BIOLOGYSCIENCENEW RESEARCH
Cancer is an adverse result of the evolution of multicellularity, a conflict between the selfish interests of malignant cells and the long-term good of the individual. It arises from successive cellular mutations to growth-regulator genes, which confer a replicative advantage to the mutated cells compared to their precursors. The chances that any one of your cells is mutated and becomes malignant is higher if you have more cells. Simply put, more cells = a higher chance that one cell becomes cancerous.
If it is not good to be larger, then the peril of developing malignancies must be incredible for the largest land animal, elephants. However, the cancer rate in elephants is lower than in humans. How is this possible? They can weigh up to 7 tons, but get less cancer than humans!
It stands to reason that these animals must have evolved mechanisms to protect themselves from the risk inherent to their size. While the forces of natural selection benefited larger body sizes, they had to develop cellular mechanisms which would prevent them from developing malignancies so that they could still survive and procreate.
Well, African and Asian elephants evolved approximately 20 extra copies of a gene called TP53, which happens to be the most commonly mutated gene in human cancers. Humans who lose TP53 function (Li-Fraumeni Syndrome) are over 20-times more likely to develop cancers.
The copy number difference in TP53 between elephants and humans could explain how elephants avoid cancer better than humans, even though their size makes them much more likely to develop cancer.
First researchers would need to demonstrate that the extra elephant genes are actually useful. In this report, researchers (including me) showed, for the first time, that expression of one extra elephant p53 protein causes cell death in human cancer cells. Of course, there are still many necessary steps between discovering that this protein can kill human cancer cells in a dish and testing whether it can kill cancer cells in humans.
I am hopeful that this work can help inform future studies about cancer resistance in humans, elephants, and all the other animals with whom we share the planet. ■
Elephants use this one neat trick to avoid tumors!