Abstract |
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 | Furong Yuan, Meizhen Chen, Peter J Hornsby |
Journal | Oncology reports
(Oncol Rep)
Vol. 23
Issue 2
Pg. 377-86
(Feb 2010)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 20043098
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Polyomavirus Transforming
- DNA-Binding Proteins
- Immunoglobulin gamma-Chains
- Rag2 protein, mouse
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Topics |
- 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)
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