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Cancer induction by restriction of oncogene expression to the stem cell compartment

AuthorsPérez-Caro, M.; Cobaleda, César ; González-Herrero, Inés ; Vicente-Dueñas, Carolina ; Bermejo-Rodríguez, C. ; Sánchez-Beato, Margarita; Orfao, Alberto ; Pintado, Belén; Flores, Teresa; Sánchez-Martín, M.; Jiménez, Rafael
Issue Date2009
PublisherNature Publishing Group
CitationEMBO Journal 28: 8-20 (2009)
AbstractIn human cancers, all cancerous cells carry the oncogenic genetic lesions. However, to elucidate whether cancer is a stem cell-driven tissue, we have developed a strategy to limit oncogene expression to the stem cell compartment in a transgenic mouse setting. Here, we focus on the effects of the BCR-ABLp210 oncogene, associated with chronic myeloid leukaemia (CML) in humans. We show that CML phenotype and biology can be established in mice by restricting BCR-ABLp210 expression to stem cell antigen 1 (Sca1)+ cells. The course of the disease in Sca1-BCR-ABLp210 mice was not modified on STI571 treatment. However, BCR-ABLp210-induced CML is reversible through the unique elimination of the cancer stem cells (CSCs). Overall, our data show that oncogene expression in Sca1+ cells is all that is required to fully reprogramme it, giving rise to a full-blown, oncogene-specified tumour with all its mature cellular diversity, and that elimination of the CSCs is enough to eradicate the whole tumour. © 2009 European Molecular Biology Organization | Some Rights Reserved.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.
Identifiersdoi: 10.1038/emboj.2008.253
issn: 0261-4189
e-issn: 1460-2075
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