| Fibroblasts from Werner syndrome patients: cancer cells derived by experimental introduction of oncogenes maintain malignant properties despite entering crisis. | |
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MedLine Citation:
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PMID: 20043098 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Werner syndrome (WS) results from defects in the gene encoding WRN RecQ helicase. WS fibroblasts undergo premature senescence in culture. Because cellular senescence is a tumor suppressor mechanism, we examined whether WS fibroblasts exhibited reduced tumorigenicity, in comparison to control cells, in a model of experimental conversion of normal human cells to cancer cells. The combination of oncogenic Ras (Ha-Ras(V12G)) and SV40 large T antigen (SV40 LT) causes human cells to acquire neoplastic properties in the absence of telomerase. We found that WS cells could also be converted to a tumorigenic state by these oncogenes, as evidenced by invasion and metastasis of cells implanted in immunodeficient mice. Ras/SV40 LT-expressing cells retained invasiveness and malignant properties even when cells reached crisis in tumors in vivo. High levels of gelatinase were found by an in situ assay in Ras/SV40 LT-expressing cells undergoing crisis. We conclude that, despite evidence of accelerated senescence in WS cells, there is no evidence that the absence of active WRN acts as a barrier to neoplastic transformation. Moreover, we find that tumorigenic human cells retain malignant properties of the cells as they approach and reach crisis. |
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Authors:
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Furong Yuan; Meizhen Chen; Peter J Hornsby |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncology reports Volume: 23 ISSN: 1791-2431 ISO Abbreviation: Oncol. Rep. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2009-12-31 Completed Date: 2010-03-30 Revised Date: 2011-09-22 |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: Greece |
Other Details:
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Languages: eng Pagination: 377-86 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78245, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Polyomavirus Transforming / genetics, physiology Cell Transformation, Neoplastic / genetics, pathology* Cells, Cultured DNA-Binding Proteins / genetics Disease Progression Female Fibroblasts / pathology* Genes, ras / physiology Graft Survival Humans Immunoglobulin gamma-Chains / genetics Male Mice Mice, Knockout Neoplasm Transplantation Neoplasms, Experimental / genetics, pathology* Oncogenes / physiology Transplantation, Heterologous Werner Syndrome / pathology* |
| Grant Support | |
ID/Acronym/Agency:
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AG12287/AG/NIA NIH HHS; AG20752/AG/NIA NIH HHS; P01 AG020752-020006/AG/NIA NIH HHS; P30 CA54174/CA/NCI NIH HHS; R37 AG012287-14/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Polyomavirus Transforming; 0/DNA-Binding Proteins; 0/Immunoglobulin gamma-Chains; 0/Rag2 protein, mouse |
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