Senescence induced by repression of human papillomavirus oncogenes in cervical cancer cells
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 replicative 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 advantages of this system compared to replicative senescence.