Although a great deal of evidence links inactivated p53 to cancer, researchers were unsure whether turning the tumor suppressor gene back on would actually halt tumor growth once it was under way.“p53 mutations could simply set the stage for other [cancer-causing] mutations,” says Tyler Jacks of the Massachusetts Institute of Technology in Cambridge. If so, he adds,“you could put p53 back into cancer cells, and the cells would simply laugh.” There was also the possibility that tumors could lose other proteins needed for normal p53 pathway function, and that these would need repair, too.

Three independent teams, one led by Jacks and the others by Gerard Evan of the University of California, San Francisco, and Scott Lowe of Cold Spring Harbor Laboratory in New York, have now found that p53 reactivation can indeed halt tumor growth.(Evan’s results appeared in the 29 December 2006 issue of Celland those of Jacks and Lowe were published online by Nature on 24 January and also appear in the 8 February issue.) Both Evan’s and Jacks’s teams used mice that had been genetically engineered so that the p53 gene could be turned on and off at will in the animals’ cells. The mice also carried oncogene mutations to facilitate the development of cancers—lymphoma in the case of the Evan team’s mice, and lymphomas and sarcomas in the Jacks team’s animals. Lowe and his team took a somewhat different tack, genetically engineering liver tumor cells so that the researchers could turn the cells’ p53 gene on and off. These cells were then transplanted into the livers of mice. In all cases, the researchers kept the p53 gene “off” until the tumors grew to an advanced stage in the animals. Then, they turned the gene back on.“We all came to the same conclusion.… When p53 is restored to the system,[cancer] cells respond,” Jacks says. Depending on the tumor type, the exact mode of the responses differed, however. The lymphoma cells in the Evan team’s mice died by apoptosis, with the tumors beginning to shrink in about 12 hours.“The effect on the tumor appears to be quite catastrophic,” Evan says. The effect was not permanent, however. Eventually the tumors grew back in all the animals, and this time p53 could not be reactivated, either because that gene or the one for a protein called MDM2 that’s known to inhibit p53 had been