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Cancer induction by restriction of oncogene expression to the stem cell compartment
Author(s) -
PérezCaro María,
Cobaleda César,
GonzálezHerrero Inés,
VicenteDueñas Carolina,
BermejoRodríguez Camino,
SánchezBeato Margarita,
Orfao Alberto,
Pintado Belén,
Flores Teresa,
SánchezMartín Manuel,
Jiménez Rafael,
Piris Miguel A,
SánchezGarcía Isidro
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.253
Subject(s) - biology , cancer , oncogene , compartment (ship) , stem cell , cancer research , cancer stem cell , microbiology and biotechnology , genetics , cell cycle , oceanography , geology
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.