Mechanism of immortalization.

Model systems implementing various approaches to immortalize cells have led toward further understanding of replicative senescence and carcinogenesis. Human diploid cells have a limited life span, termed replicative senescence. Because cells are terminally growth arrested during replicative senescence, it has been suggested that it acts as a tumor suppression mechanism as tumor cells exhibit an indefinite life span and are immortal. The generation of immortal cells lines, by the introduction of SV40 and human papillomavirus (HPV) sequences into cells, has provided invaluable tools to dissect the mechanisms of immortalization. We have developed matched sets of nonimmortal and immortal SV40 cell lines which have been useful in the identification of novel growth suppressor genes (SEN6) as well as providing a model system for the study of processes such as cellular aging, apoptosis, and telomere stabilization. Thus, their continued use is anticipated to lead to insights into other processes, which are effected by the altered expression of oncogenes and growth suppressors.