Abstract
Cellular senescence is a tumor-suppressor mechanism that has been shown to occur in response to multiple signals, including oncogenic stress, DNA damage, oxidative stress, telomere shortening, and other tumor-promoting insults. Over the past decade, much has been uncovered regarding the phenotype of this tumor-suppressor response and the underlying pathways necessary for its establishment. However, we have also learned that the intricate details of signaling pathways underlying senescence as a tumor-suppressor response are very much context dependent. In addition, cross-talk among pathways, and negative and positive feedback loops, all complicate our understanding of this process. This short review attempts to summarize what is known to date regarding senescence in tumor suppression, both in vitro and in vivo. Further insights into pathways necessary for senescence will hopefully identify appropriate targets for interventions to not only induce senescence as a treatment of cancerous lesions, but also to maintain this state in premalignant lesions in an effort to prevent progression to cancer.
Highlights
The phenomenon of cellular senescence was first described by Hayflick and Moorhead as a cell culture observation, where human diploid fibroblasts irreversibly exit the cell cycle after undergoing serial passage in vitro[1]
We found that by using gene expression analysis, Senescence-Associated Heterochromatin Foci (SAHF)-containing pineal cells from 2-month-old Irbp-Cyclin D1 mice differ from nonsenescent (Irbp-Cyclin D1, p53–/–) pineal cells primarily in expression of cell cycle–associated genes
Our studies showed that Cyclin D1 expression in photoreceptor progenitor cells in the neuroendocrine pineal gland results in hyperproliferation limited by both p53- and Rb-dependent senescence[10]
Summary
Received February 9, 2010; Revised March 22, 2010; Accepted March 24, 2010; Published April 13, 2010. Cellular senescence is a tumor-suppressor mechanism that has been shown to occur in response to multiple signals, including oncogenic stress, DNA damage, oxidative stress, telomere shortening, and other tumor-promoting insults. Much has been uncovered regarding the phenotype of this tumor-suppressor response and the underlying pathways necessary for its establishment. We have learned that the intricate details of signaling pathways underlying senescence as a tumorsuppressor response are very much context dependent. Cross-talk among pathways, and negative and positive feedback loops, all complicate our understanding of this process. This short review attempts to summarize what is known to date regarding senescence in tumor suppression, both in vitro and in vivo.
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