Evidence for multiple pathways to cellular senescence.

Normal cells in culture generally senesce whereas tumor-derived cells are often, but not without exception, immortal and grow indefinitely. For cells to escape the senescence program, normal genes must be lost or inactivated as shown by somatic cell genetic studies. For example, the introduction of specific chromosomes by microcell-mediated chromosome transfer has been shown to induce senescence of human and rodent tumor cell lines, and the mapping of over ten senescence genes has been achieved by this method. In this study, we observed that two different normal chromosomes induce senescence in the same human endometrial carcinoma cell line, which suggests that multiple pathways to senescence are inactivated in this cell line. This hypothesis has implications for the mechanisms of cellular senescence and its role in carcinogenesis. Furthermore, this hypothesis can explain why not all tumor-derived cells are immortal.