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Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation

AutorRubio, Daniel; García, Silvia; Paz, María F.; Cueva, Teresa de la; López-Fernández, Luis A.; Lloyd, Alison C.; García-Castro, Javier; Bernad, Antonio
Fecha de publicación2-ene-2008
EditorPublic Library of Science
CitaciónPLoS ONE. 2008; 3(1): e1398.
ResumenBackground. 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.
URIhttp://hdl.handle.net/10261/2889
DOI10.1371/journal.pone.0001398
ISSN1932-6203
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