For years, scientists have been convinced that one particular gene, dubbed p53, plays a central role in cancer. In study after study, people with breast, lung, colon, brain, and other cancers have been found to harbor defective copies of this gene. Researchers hypothesized that somehow the gene is normally able to suppress nascent tumors--but how?
Now, scientists at Johns Hopkins University have an answer. By experimenting with healthy and defective p53 genes in normal and abnormal cells, a team led by oncologist Michael Kastan discovered that the gene acts as a traffic cop: When radiation, carcinogens, or spontaneous mutations injure a cell's DNA, the p53 gene puts a temporary halt to that cell's reproduction. This gives the cell a chance to repair the damage to its genetic machinery and prevents the flaws from being passed on to progeny cells. But when p53 isn't working properly, the defective cells replicate, increasing the risk of cancer. "This provides a beautiful explanation for how p53 contributes to the development of tumors," says Kastan. It could also point the way to more effective cancer drugs.