Early in development, most human cells turn off expression of an essential component of telomerase, the enzyme responsible for aIDition of telomere repeat sequences (5′ TTAGGG 3′) to the ends of chromosomes. Thus, as our cells proliferate, their telomeres get shorter and shorter, but are normally lost over the course of a lifetime. If cells are removed from the body and grown in culture, they ultimately enter a state of replicative senescence and stop dividing when their telomeres get too short. By contrast, most tumor cells, in humans and in cell culture, express active telomerase allowing them to maintain their telomeres and grow beyond the normal limit imposed by senescence. Anticipating a universal cure for cancer, you set up a company to screen chemical ‘libraries’ for telomerase inhibitors. The company share price takes a tumble, when a rival group generates a strain of mice from which the telomerase genes have been deleted. These mice breed happily for several generations, but by the 6th generation (when their telomeres are much shorter than those of normal mice), they have a greatly increased tendency to die of tumors. The tumors tend to arise in tissues that show high proliferation rates, such as testis, skin, and blood. Why has this observation shaken the confidence of your investors? Is there a flaw in your hypothesis?
