Abstract

Human diploid cells have a limited life span, ending in replicative senescence, in contrast to cell lines derived from tumors, which show an indefinite life span and are immortal, suggesting that replicative senescence is a tumor suppression mechanism. We have utilized introduction of SV40 sequences to develop matched sets of nonimmortal and immortal cell lines to help dissect the mechanism of immortalization and have found that it has multiple facets, involving both SV40-dependent and -independent aspects. These studies have led to the identification of a novel growth suppressor gene (SEN6) as well as providing a model system for the study of cellular aging, apoptosis, and telomere stabilization among other things. It is anticipated that SV40-transformed cells will continue to provide a very useful experimental system leading to insights into the behavior of cells with altered expression of oncogenes and growth suppressor gene products.

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