Molecular Characterization of Spontaneous Mesenchymal = Stem Cell Transformation

From: Subject: Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation Date: Wed, 6 Feb 2008 11:43:08 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0015_01C868B5.71CED9D0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0015_01C868B5.71CED9D0 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2151133&rendertype=abstract =EF=BB=BF Molecular Characterization of Spontaneous Mesenchymal = Stem Cell Transformation

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	Journal=20 List > PLoS=20 ONE > v.3= (1);=20 2008
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif" = border=3D0>Abstract Full Text PDF (1.0M) Contents Archive Related=20 material: PubMed=20 articles by: Rubio, D. Garcia, S. Paz, M. Bernad, = A.		PLoS ONE. 2008; 3(1): e1398. Published online 2008 January = 2.=20 doi:=20 10.1371/journal.pone.0001398. Copyright<= /A>=20 Rubio et al. This is an open-access article distributed under the = terms of=20 the Creative Commons Attribution License, which permits = unrestricted use,=20 distribution, and reproduction in any medium, provided the = original author=20 and source are credited. Molecular Characterization of Spontaneous = Mesenchymal=20 Stem Cell Transformation Daniel=20 Rubio,¹^=C2=A4a Silvia = Garcia,¹^=C2=A4b=20 Maria F. Paz,¹^=C2=A4b Teresa De la=20 Cueva,¹^=C2=A4c Luis A. = Lopez-Fernandez,²=20 Alison C. Lloyd,³ Javier=20 Garcia-Castro,^1,⁴ and Antonio=20 Bernad¹^^=C2=A4b ¹Department of Immunology and = Oncology,=20 Centro Nacional de Biotecnolog=C3=ADa, Consejo Superior de = Investigaciones=20 Cient=C3=ADficas (CSIC), Universidad Aut=C3=B3noma de Madrid, = Madrid, Spain ²Servicio de Farmacia, Hospital = General=20 Universitario Gregorio Mara=C3=B1=C3=B3n, Madrid, Spain ³Laboratory for Molecular Cell = Biology,=20 University College London, London, United Kingdom ⁴Andalusian Stem Cell Bank, = Granada,=20 Spain Joseph Najbauer, Academic=20 Editor City of Hope Medical Center, United States of = America To whom correspondence should = be=20 addressed. E-mail: abernad/at/cnic.es Conceived and designed the experiments: = DR AB JG.=20 Performed the experiments: DR SG TD MP. Analyzed the data: DR SG = AL JG LL.=20 Contributed reagents/materials/analysis tools: AL. Wrote the = paper: DR AB=20 AL JG. ^=C2=A4aCurrent = address: Centro de=20 Biolog=C3=ADa Molecular Severo Ochoa, Universidad Aut=C3=B3noma de = Madrid, Madrid,=20 Spain ^=C2=A4bCurrent = address: Department of=20 Regenerative Cardiology, Centro Nacional de Investigaciones=20 Cardiovasculares (CNIC), Madrid, Spain ^=C2=A4cCurrent = address: Animalary=20 facility, Centro Nacional de Servicio de Biotecnolog=C3=ADa, = Consejo Superior=20 de Investigaciones Cient=C3=ADficas (CSIC), Universidad = Aut=C3=B3noma de Madrid,=20 Madrid, Spain Received November 23, 2006; Accepted = December 7,=20 2007.
	Abstract Background We = previously=20 reported the in vitro spontaneous transformation of human = mesenchymal stem cells (MSC) generating a population with = tumorigenic=20 potential, that we termed transformed mesenchymal cells (TMC). Methodology/Principal=20 Findings Here we have characterized the molecular changes = associated=20 with TMC generation. Using microarrays techniques we identified a = set of=20 altered pathways and a greater number of downregulated than = upregulated=20 genes during MSC transformation, in part due to the expression of = many=20 untranslated RNAs in MSC. Microarray results were validated by = qRT-PCR and=20 protein detection. Conclusions/Significance In our=20 model, the transformation process takes place through two = sequential=20 steps; first MSC bypass senescence by upregulating c-myc and = repressing=20 p16 levels. The cells then bypass cell crisis with acquisition of=20 telomerase activity, Ink4a/Arf locus deletion and Rb = hyperphosphorylation.=20 Other transformation-associated changes include modulation of=20 mitochondrial metabolism, DNA damage-repair proteins and cell = cycle=20 regulators. In this work we have characterized the molecular = mechanisms=20 implicated in TMC generation and we propose a two-stage model by = which a=20 human MSC becomes a tumor cell.
	Articles=20 from PLoS ONE = are provided=20 here courtesy of Public Library of Science Write = to=20 PMC \| PMC = Home \| PubMed NCBI \| U.S. National Library of = Medicine NIH \| Department of Health and = Human=20 Services Privac= y=20 Policy \| Disclaimer= \| Freedom of=20 Information=20 Act

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