When the researchers reactivated p53 in the mice they found that the liver tumors completely disappeared. "This was quite surprising," said Lowe. "We were working with a very advanced, aggressive tumor, but when we reestablished p53, not only did it stop growing, it went away.
"But the second surprise—and perhaps the more scientifically interesting one—was why the tumor went away," said Lowe.
"We expected the tumor cells to undergo programmed cell death, or apoptosis. But instead, we saw evidence for a very different process that p53 also regulates—senescence, or growth arrest. What really excited us was evidence that this senescence somehow triggered the innate immune system to kill the tumor cells." Involvement of the innate immune system suggests there may be an unknown mechanism by which cancers can trigger the immune system, he said. Lowe and his colleagues are now exploring how the innate immune system might be enlisted against cancer.
Jacks's team used a different technique to reactivate p53 in lymphomas and sarcomas. In their experiments, the researchers produced mice whose cells did not have p53 activity. These mice were genetically engineered so that the drug tamoxifen could be used to switch on p53 activity.
"When we reactivated p53 in these mice, we saw two distinct tumor phenotypes," said Jacks. "In lymphomas the responses were rapid, extensive and were accompanied by the induction of apoptosis. In the sarcomas, the response was less rapid ofte
Source:Howard Hughes Medical Institute