Jan 25, 2007
A tumour in a mouse shrank after the gene was reactivated
Many cancers are believed to result from a defect in the tumour-suppressing gene p53.
Two groups of US researchers reactivated the gene in the lab, and found that was enough to make various types of tumour start to shrink.
The Nature studies raise hopes of a new generation of anti-cancer drugs that work by boosting p53 activity.
The p53 gene is mutated or inactivated in most human cancers.
It is one of the most widely studied genes in cancer, and researchers have identified compounds that restore its function.
But until now, it has not been known whether such activity would actually reverse tumour growth in established tumours.
Two groups, from New York's Cold Spring Harbor Laboratory and the Massachusetts Institute of Technology (MIT) in Cambridge, appear to have provided the answer.
In animal experiments, they showed that even briefly reactivated, the gene dramatically reduces the size of the tumours, in some cases by 100%.
The mechanism behind the regression appears to vary depending on the type of tumour.
The MIT team found that lymphoma cells are coaxed to commit suicide, while sarcoma (a cancer of the connective tissue) cells start to grow old, and lose their ability to divide.
The New York team, working with a liver tumour, found that the cellular ageing provoked by p53 was linked to an immune system response, which saw an increase in activity in molecules that help to clear the cancer cells away.
The researchers are not sure why these two cancers are affected in different ways, but have started trying to identify the other genes that are activated in each type of tumour when p53 turns back on.
Dr Andrea Ventura, a member of the MIT team, said: "This study provides critical genetic evidence that continuous repression of a tumour suppressor gene is required for a tumour to survive."
In normal cells, p53 controls the cell cycle. When functioning properly, it activates DNA repair mechanisms and prevents cells with damaged DNA from dividing.
If DNA damage is irreparable, p53 induces the cell to destroy itself by undergoing apoptosis, or programmed cell death.
When p53 is turned off by mutation or deletion, cells are much more likely to become cancerous, because they will divide uncontrollably even when DNA is damaged.
The researchers used engineered mice that had the gene for p53 turned off.
But, they also included a genetic "switch" that allowed the researchers to turn p53 back on after tumours developed.
The study also revealed that turning on p53 has no damaging effects in normal cells.
The researchers had worried that p53 would kill normal cells because it had never been expressed in those cells.
Ed Yong, of the charity Cancer Research UK, said: "It is very encouraging that cancers in mice can be treated by turning p53 back on.
"Since p53 is commonly switched off in human cancers, reactivating it could potentially provide a powerful way of treating the disease in the future.
"But before this can happen, scientists need to show that the same strategy could work in human cancers."