GENETIC CHANGES ASSOCIATED WITH IMMORTALIZATION - A REVIEW

Human fibroblasts appear to have three terminal proliferative arrest ( TPA) states that act as independent barriers to immortalization. The f irst of these TPA states is senescence, and several recent studies hav e shown that abrogation of p53 function permits temporary escape from senescence that ends in a poorly characterized form of arrest (referre d to as p53-minus TPA) in which the pRB and p16(INK4) genes appear to be involved. Abrogation of the function of both p53 and pRB (or p16(IN K4)) results in continued proliferation until the cells enter crisis. Escape from crisis is always associated with the activation of a telom ere maintenance mechanism. We also review evidence for the involvement of other genes in the immortalization process. Immortalization appear s to be a samples process involving many genetic changes, not all of w hich are necessarily related to telomere maintenance.