ABSTRACT
The study of tumor viruses has provided many insights into fundamental cellular
processes including cell-cycle control, signal transduction, proliferation, and
apoptosis. Another important but poorly understood cellular process is repli-
cative senescence, a permanent growth-arrested state attained by normal somatic
cells after extended continuous passage in culture. Senescence is regarded as an
important tumor suppressor mechanism and model of cellular aging (1).
Unfortunately, replicative senescence is difficult to study because it develops in
heterogenous populations of cells after several months of continuous passage.
Viral oncogenes can allow cultured cells to escape replicative senescence and
proliferate indefinitely, a process called cell immortalization, suggesting that
studies of tumor viruses will provide insight into senescence. This chapter
reviews a novel method of inducing senescence rapidly and synchronously by
extinction of the expression of human papillomavirus (HPV) oncogenes in
human cervical carcinoma cells. This chapter also describes some of the essential
cellular and biochemical features of this model and discusses technical advan-
tages of this system compared to replicative senescence.
