THE DYNAMIC SYSTEM [TELOMERES-TELOMERASE-PROLIFERATION] UNDERLIES PERENNIAL GROWTH OF CANCER CELLS AND EPISODES OF DRUG RESISTANCE

For a long time, regular progressive growth and resistance to anticancer drugs have been considered as invariant characteristics of a tumor. However, there are indications that both cell growth and drug resistance can display discontinuous patterns over months, although the mechanisms underlying these fluctuations are unclear. Our hypothesis is that telomere regulation plays an important role in such fluctuations. In rat hepatocarcinoma cells in vitro, we observed that every part of the small complex system [Telomeres-Telomerase-Proliferation] displayed deterministic oscillations. These oscillations were coordinated and resulted in an oscillatory conservative behavior of the whole system. This global dynamic equilibrium was found critical for perennial growth of hepatocarcinoma cells and for peaks of cell resistance to methotrexate.