Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82453
Title:
Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence.
Authors:
Barradas, Marta; Gonos, Efstathios S; Zebedee, Zoe; Kolettas, Evangelos; Petropoulou, Charikleia; Delgado, M Dolores; León, Javier; Hara, Eiji; Serrano, Manuel
Abstract:
Normal cells display protective responses against oncogenes. Notably, oncogenic Ras triggers an irreversible proliferation arrest that is reminiscent of replicative senescence and that is considered a relevant tumor-suppressor mechanism. Here, we have used microarrayed filters to identify genes specifically upregulated in Ras-senescent human fibroblasts. Among the initial set of genes selected from the microarrays, we found the cell-cycle inhibitor p21(Cip1/Waf1), thus validating the potency of the screening to identify markers and mediators of Ras-senescence. A group of six genes, formed by those more highly upregulated during Ras-senescence, was analyzed in further detail to evaluate their specificity. In particular, we examined their expression in cells overexpressing Ras but rendered resistant to Ras-senescence by the viral oncoprotein E1a; also, we have studied their expression during replicative senescence, organismal aging, H(2)O(2)-induced senescence, and DNA damage. In this manner, we have identified a novel gene, RIS1 (for Ras-induced senescence 1), which is not upregulated in association to any of the above-mentioned processes, but exclusively during Ras-senescence. Furthermore, RIS1 is also upregulated by the transcriptional factor Ets2, which is a known mediator of Ras-induced senescence. Interestingly, RIS1 is located at chromosomal position 3p21.3 and, more specifically, it is included in a short segment of just 1 Mb previously defined by other investigators for its tumor-suppressor activity. In summary, we report the identification of a novel gene, RIS1, as a highly specific marker of Ras-induced senescence and a candidate tumor-suppressor gene.
Affiliation:
Department of Immunology and Oncology, Spanish National Center of Biotechnology (CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.
Citation:
Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence. 2002, 273 (2):127-37 Exp. Cell Res.
Journal:
Experimental Cell Research
Issue Date:
15-Feb-2002
URI:
http://hdl.handle.net/10541/82453
DOI:
10.1006/excr.2001.5434
PubMed ID:
11822868
Type:
Article
Language:
en
ISSN:
0014-4827
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBarradas, Marta-
dc.contributor.authorGonos, Efstathios S-
dc.contributor.authorZebedee, Zoe-
dc.contributor.authorKolettas, Evangelos-
dc.contributor.authorPetropoulou, Charikleia-
dc.contributor.authorDelgado, M Dolores-
dc.contributor.authorLeón, Javier-
dc.contributor.authorHara, Eiji-
dc.contributor.authorSerrano, Manuel-
dc.date.accessioned2009-09-24T08:31:24Z-
dc.date.available2009-09-24T08:31:24Z-
dc.date.issued2002-02-15-
dc.identifier.citationIdentification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence. 2002, 273 (2):127-37 Exp. Cell Res.en
dc.identifier.issn0014-4827-
dc.identifier.pmid11822868-
dc.identifier.doi10.1006/excr.2001.5434-
dc.identifier.urihttp://hdl.handle.net/10541/82453-
dc.description.abstractNormal cells display protective responses against oncogenes. Notably, oncogenic Ras triggers an irreversible proliferation arrest that is reminiscent of replicative senescence and that is considered a relevant tumor-suppressor mechanism. Here, we have used microarrayed filters to identify genes specifically upregulated in Ras-senescent human fibroblasts. Among the initial set of genes selected from the microarrays, we found the cell-cycle inhibitor p21(Cip1/Waf1), thus validating the potency of the screening to identify markers and mediators of Ras-senescence. A group of six genes, formed by those more highly upregulated during Ras-senescence, was analyzed in further detail to evaluate their specificity. In particular, we examined their expression in cells overexpressing Ras but rendered resistant to Ras-senescence by the viral oncoprotein E1a; also, we have studied their expression during replicative senescence, organismal aging, H(2)O(2)-induced senescence, and DNA damage. In this manner, we have identified a novel gene, RIS1 (for Ras-induced senescence 1), which is not upregulated in association to any of the above-mentioned processes, but exclusively during Ras-senescence. Furthermore, RIS1 is also upregulated by the transcriptional factor Ets2, which is a known mediator of Ras-induced senescence. Interestingly, RIS1 is located at chromosomal position 3p21.3 and, more specifically, it is included in a short segment of just 1 Mb previously defined by other investigators for its tumor-suppressor activity. In summary, we report the identification of a novel gene, RIS1, as a highly specific marker of Ras-induced senescence and a candidate tumor-suppressor gene.en
dc.language.isoenen
dc.subjectTumor Suppressor Genesen
dc.subjectTumour Suppressor Proteinsen
dc.subject.meshAdenovirus E1A Proteins-
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshCell Aging-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshChild-
dc.subject.meshDNA Damage-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshGenes, Tumor Suppressor-
dc.subject.meshHumans-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshMembrane Proteins-
dc.subject.meshMiddle Aged-
dc.subject.meshProto-Oncogene Protein c-ets-2-
dc.subject.meshProto-Oncogene Proteins-
dc.subject.meshRepressor Proteins-
dc.subject.meshTrans-Activators-
dc.subject.meshTranscription Factors-
dc.subject.meshTranscriptional Activation-
dc.subject.meshTumor Suppressor Proteins-
dc.subject.meshUp-Regulation-
dc.subject.meshras Proteins-
dc.titleIdentification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence.en
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology and Oncology, Spanish National Center of Biotechnology (CSIC), Campus de Cantoblanco, Madrid E-28049, Spain.en
dc.identifier.journalExperimental Cell Researchen

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