Background. We previously reported the in vitro spontaneous transformation of human mesenchymal stem cells (MSC) generating a population with tumorigenic potential, that we termed transformed mesenchymal cells (TMC). Methodology/Principal Findings. Here we have characterized the molecular changes associated with TMC generation. Using microarrays techniques we identified a set of altered pathways and a greater number of downregulated than upregulated genes during MSC transformation, in part due to the expression of many untranslated RNAs in MSC. Microarray results were validated by qRT-PCR and protein detection. Conclusions/Significance. In our model the transformation process takes place through two sequential steps; first MSC bypass senescence by upregulating c-myc and repressing p16 levels, The cells then bypass cell crisis with acquisition of telomerase activity, ink4a/Arf locus deletion and Rb hyperphosphorylation. Other transformation-associated changes include modulation of mitochondrial metabolism, DNA damage-repair proteins and cell cycle regulators. In this work we have characterized the molecular mechanisms implicated in TMC generation and we propose a two-stage model by which a human MSC becomes a tumor cell. © 2008 Rubio et al.
CITATION STYLE
Rubio, D., Garcia, S., Paz, M. F., de la Cueva, T., Lopez-Fernandez, L. A., Lloyd, A. C., … Bernard, A. (2008). Molecular characterization of spontaneous mesenchymal stem cell transformation. PLoS ONE, 3(1). https://doi.org/10.1371/journal.pone.0001398
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