Molecular Biology, Telomeres and Tumors

Question

Early in development, most human cells turn off expression of an essential component of telomerase, the enzyme responsible for addition of telomere repeat sequences (5’-TTAGGG) to the ends of chromosomes. Thus, as our cells proliferate their telomeres get shorter and shorter, but are normally not lost over the course of a lifetime. If cells are removed from the body and grown in culture, however they ultimately enter a state of replicative senescence and stop dividing when their telomeres get too short. By contrast, most human tumor cells express active telomerase, allowing them to maintain their telomeres and grow beyond the normal limit imposed by senescence - good for them, bad for us.

            Anticipating a universal cure for cancer, you set up a company to screen chemical ‘libraries’ for telomerase inhibitors. The company share price takes a dive, however, when a rival group generates a strain of telomerase-knockout mice. These mice breed happily for several generations, but by the sixth generation (when their telomeres are much shorter than normal) they have a greatly increased tendency to die of tumors, compared to their normal-telomerase littermates. 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 the investors? Is there a flaw in your hypothesis?

Answer 1

With this question, you would want to understand what the role of the "strain of telomerase-knockout" is and its relationship with a tumor development. When the mice gene get altered by a strain of telomerase-knockout, it means that the coding strain for telomerase do not present in the mice gene anymore. The hypothesis here is that the telomerase strain could be the reason for the tumor development and without the telomerase, mice will be less likely to have tumors. However, the experiment on mice not having the telomerase sequence does not show so. Mice still develop tumors in their later cell division cycles as usual. It proves that the hypothesis was not true and the investor may have invested in a wrong project.