ABSTRACT
Replicative senescence is thought to be an intrinsic mechanism for limiting the proliferative life-span of normal somatic cells. We show here that rat Schwann cells can be expanded indefinitely in culture while maintaining checkpoints normally lost during the immortalization process. These findings demonstrate that senescence is not an inevitable consequence of extended proliferation in culture.
Subject(s)
Cell Division , Cellular Senescence , Schwann Cells/cytology , Animals , Blood , Carrier Proteins/metabolism , Cell Culture Techniques , Cell Line , Cell Size , Cells, Cultured , Clone Cells , Culture Media , Cyclin-Dependent Kinase Inhibitor p16 , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , Fibroblasts/cytology , Fibroblasts/physiology , Giant Cells/cytology , Mutation , Phenotype , Proteins/metabolism , Rats , Schwann Cells/physiology , Telomerase/metabolism , Telomere/physiology , Tumor Suppressor Protein p14ARF , Tumor Suppressor Protein p53/metabolism , beta-Galactosidase/metabolism , ras Proteins/metabolismABSTRACT
Historically, the senescent state has been associated with, and was named after, the cell-cycle arrest that occurs after cells have undergone an intrinsically defined number of divisions in vitro. More recently, however, it has been shown that extrinsic factors, including those encountered in normal tissue-culture environments, can prematurely induce an indistinguishable senescent phenotype. In this review, we discuss the pathways of cell senescence, the mechanisms involved and the role that these pathways have in regulating the initiation and progression of cancer.
