Rapid induction of senescence in human cervical carcinoma cells

Expression of the bovine papillomavirus E2 regulatory protein in human cerv ical carcinoma cell lines repressed expression of the resident human papill omavirus E6 and E7 oncogenes and within a few days caused essentially all o f the cells to synchronously display numerous phenotypic markers characteri stic of cells undergoing replicative senescence. This process was accompani ed by marked but in some cases transient alterations in the expression of c ell cycle regulatory proteins and by decreased telomerase activity. We prop ose that the human papillomavirus E6 and E7 proteins actively prevent senes cence from occurring in cervical carcinoma cells, and that once viral oncog ene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.