title: Cancer induction by restriction of oncogene expression to the stem cell compartment.
abstract: 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.
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pérez-Caro
authors.forename: César
authors.initials: C
authors.lastname: Cobaleda
authors.forename: Inés
authors.initials: I
authors.lastname: González-Herrero
authors.forename: Carolina
authors.initials: C
authors.lastname: Vicente-Dueñas
authors.forename: Camino
authors.initials: C
authors.lastname: Bermejo-Rodríguez
authors.forename: Margarita
authors.initials: M
authors.lastname: Sánchez-Beato
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Belén
authors.initials: B
authors.lastname: Pintado
authors.forename: Teresa
authors.initials: T
authors.lastname: Flores
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Martín
authors.forename: Rafael
authors.initials: R
authors.lastname: Jiménez
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Isidro
authors.initials: I
authors.lastname: Sánchez-García
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D015870:Gene Expression; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D013234:Stem Cells; D016019:Survival Analysis
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins