المستودع الأكاديمي جامعة المدينة

Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation

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dc.creator Rubio, Daniel
dc.creator García, Silvia
dc.creator Paz, María F.
dc.creator Cueva, Teresa de la
dc.creator López-Fernández, Luis A.
dc.creator Lloyd, Alison C.
dc.creator García-Castro, Javier
dc.creator Bernad, Antonio
dc.date 2008-02-07T00:09:08Z
dc.date 2008-02-07T00:09:08Z
dc.date 2008-01-02
dc.date.accessioned 2017-01-31T01:00:00Z
dc.date.available 2017-01-31T01:00:00Z
dc.identifier PLoS ONE. 2008; 3(1): e1398.
dc.identifier 1932-6203
dc.identifier http://hdl.handle.net/10261/2889
dc.identifier 10.1371/journal.pone.0001398
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/2889
dc.description 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).
dc.description 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.
dc.description 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.
dc.description DR and SG received predoctoral fellowships from the Spanish Ministry of Education and Science, JG-C and L L-F received postdoctoral fellowships from the Ministry of Science and Technology and the Ministerio de Sanidad y Consumo (FIS; CP03/0031 and CP06/0267). This work was partially supported by Spanish Ministry of Science and Technology (CICYT) grants SAF2001-2262, SAF2005-0864 and GEN2001-4856-C13-02 to AB. The Department of Immunology and Oncology was founded and is supported by the Spanish National Research Council (CSIC) and by Pfizer.
dc.description Peer reviewed
dc.format 1055768 bytes
dc.format application/pdf
dc.language eng
dc.publisher Public Library of Science
dc.relation Publisher’s version
dc.rights openAccess
dc.title Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation
dc.type Artículo


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