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

• María Pérez-Caro ^[1] ; César Cobaleda ^[2] ; Inés González-Herrero ^[1] ; Carolina Vicente-Dueñas ^[1] ; Camino Bermejo-Rodríguez ^[1] ; Margarita Sánchez-Beato ^[3] ; Alberto Orfao ^[2] ; Belén Pintado ^[4] ; Teresa Flores ^[2] ; Manuel Sánchez-Martín ^[2] ; Rafael Jiménez Fernández ^[1] ; Miguel A Piris ^[3] ; Isidro Sánchez-García ^[1]
  1. [1] Instituto de Biología Molecular y Celular del Cáncer de Salamanca / Centro de Investigación del Cáncer

     Instituto de Biología Molecular y Celular del Cáncer de Salamanca / Centro de Investigación del Cáncer

     Salamanca, España

     
  2. [2] Universidad de Salamanca

     Universidad de Salamanca

     Salamanca, España

     
  3. [3] Centro Nacional de Investigaciones Oncológicas

     Centro Nacional de Investigaciones Oncológicas

     Madrid, España

     
  4. [4] Genetically Engineered Mouse Facility, CNB-CSIC, Madrid, Spain

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 28, Nº. 1, 2008, págs. 8-20
• Idioma: inglés
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• Resumen

  • In 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.