Dissecting the senescence-like program in tumor cells activated by Ras signaling

Bihani, Teeru, Chicas, Agustin, Lo, Crystal Pui-Kwan, Lin, Athena W. (January 2007) Dissecting the senescence-like program in tumor cells activated by Ras signaling. Journal of Biological Chemistry, 282 (4). pp. 2666-2675. ISSN 0021-9258

URL: https://www.ncbi.nlm.nih.gov/pubmed/17135242
DOI: 10.1074/jbc.M608127200

Abstract

Activated Ras signaling can induce a permanent growth arrest in osteosarcoma cells. Here, we report that a senescence-like growth inhibition is also achieved in human carcinoma cells upon the transduction of H-Ras(V12). Ras-induced tumor senescence can be recapitulated by the transduction of activated, but not wild-type, MEK. The ability for H-Ras(V12) to suppress tumor cell growth is drastically compromised in cells that harbor endogenous activating ras mutations. Notably, growth inhibition of tumor cells containing ras mutations can be achieved through the introduction of activated MEK. Tumor senescence induced by Ras signaling can occur in the absence of p16 or Rb and is not interrupted by the inactivation of Rb, p107, or p130 via short hairpin RNA or the transduction with HPV16 E7. In contrast, inactivation of p21 via short hairpin RNA disrupts Ras-induced tumor senescence. In summary, this study uncovers a senescence-like program activated by Ras signaling to inhibit cancer cell growth. This program appears to be intact in cancer cells that do not harbor ras mutations. Moreover, cancer cells that carry ras mutations remain susceptible to tumor senescence induced by activated MEK. These novel findings can potentially lead to the development of innovative cancer intervention.

Item Type: Paper
Uncontrolled Keywords: Human diploid fibroblasts OF-FUNCTION MUTATIONS cellular senescence HUMAN CANCER retinoblastoma cancer PREMATURE SENESCENCE DNA-DAMAGE heterchromatin formation REPLICATIVE SENESCENCE GAMMA-IRRADIATION
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > RAS
diseases & disorders > cancer > cancer types > ostiosarcoma
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation > transduction
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation > transduction
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: January 2007
Date Deposited: 02 Dec 2011 17:58
Last Modified: 21 Mar 2018 15:02
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22969

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