Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a

Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., Lowe, S. W. (March 1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell, 88 (5). pp. 593-602. ISSN 0092-8674 (Print)

Abstract

Oncogenic ras can transform most immortal rodent cells to a tumorigenic state. However, transformation of primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16. Here we show that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest. The arrest induced by ras is accompanied by accumulation of p53 and p16, and is phenotypically indistinguishable from cellular senescence. Inactivation of either p53 or p16 prevents ras-induced arrest in rodent cells, and E1A achieves a similar effect in human cells. These observations suggest that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an oncogenic stimulus. Negation of ras-induced senescence may be relevant during multistep tumorigenesis.

Item Type:	Paper
Uncontrolled Keywords:	Animals Biological Markers Blotting, Northern CDC2-CDC28 Kinases Carrier Proteins/ metabolism Cell Aging/genetics Cell Cycle Proteins/metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinases/metabolism Enzyme Inhibitors/metabolism Fibroblasts/cytology/enzymology Gene Expression Regulation, Neoplastic/physiology Genes, Tumor Suppressor Humans Immunoblotting Mice Mice, Mutant Strains Oncogenes/ genetics Protein-Serine-Threonine Kinases/metabolism RNA, Messenger/analysis Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Transformation, Genetic Tumor Suppressor Protein p53/ metabolism ras Proteins/ genetics
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:	Beach, David H. Lin, Athena W. Lowe, Scott W. McCurrach, Mila E.
Communities:	CSHL labs > Beach lab CSHL labs > Lowe lab
Depositing User:	Kathleen Darby
Date:	7 March 1997
Date Deposited:	08 May 2014 16:13
Last Modified:	08 May 2014 16:13
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/29972

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