puzzle of p53 behavior. Lack of “puma” protein should have caused cancer to be pervasive but it has the opposite effect. What gives? Nature has a way of surprising you when you think you got it all understood. Complex systems are complex for this reason and whenever, we simplify the model, it’s like seeing non-linear systems through approximation of linear system.
“It seemed a good way to give a Ph.D. student a solid, but not overly exciting paper,” says Andreas Strasser, a cancer biologist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, who led one of the groups.
Instead of being riddled with cancer, mice lacking Puma “got no tumors at all” after repeated rounds of radiation exposure, Strasser says.
Under normal conditions, radiation causes so much damage to DNA that blood cells can’t cope and turn on Puma’s cell-suicide program. In that way, about 80 percent of mature blood cells die after a massive dose of radiation.
Surviving stem cells have to “first deal with the DNA damage from radiation, and then they have to expand [their numbers] and regenerate like crazy making new blood cells to save the animal from anemia,” says Villunger. The pressure to reproduce many blood cells quickly puts stress on stem cells and may result in mutations that could lead to cancer the next time stem cells have to work that hard.
Stem cells in mice lacking Puma are spared from the heavy work load, because mature cells survive the radiation onslaught. When Strasser’s group killed off mature blood cells in the mice lacking Puma with drugs called glucocorticoids, the mice got lymphoma, indicating that it’s the initial apoptosis-induced die-off of mature cells and subsequent overworking and overstressing of stem cells that causes the cancer.