Journal
EMBO JOURNAL
Volume 28, Issue 1, Pages 8-20Publisher
WILEY
DOI: 10.1038/emboj.2008.253
Keywords
cancer; cancer stem cells (CSCs); CSC inhibitors; drug discovery; mouse models
Categories
Funding
- FEDER
- MEC [SAF2006-03726]
- Junta de Castilla y Leon [CSI13A08, GR15, SA087A06, SA085A06]
- FIS [PI050087, PI041271]
- Federacion de Cajas de Ahorro Castilla y Leon (I Convocatoria de Ayudas para Proyectos de Investigacion Biosanitaria con Celulas Madre)
- CDTEAM [CENIT-Ingenio 2010]
- MEC OncoBIO Consolider-Ingenio 2010 [CSD2007-0017]
- Fondo de Investigaciones Sanitarias [PI04/0261, PI080164]
- Fundacion de Investigacion Medica MM
- Spanish Ministerio de Educacion y Ciencia
- Instituto de Salud Carlos III
- Ministerio de Sanidad y Consumo, Madrid, Spain [IISCIII-RTICC RD06/0020/0035-FEDER]
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available