Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells.
Details
Publication Year 2014-02, Volume 6, Issue #2, Page 212-25
Journal Title
EMBO molecular medicine
Publication Type
Journal Article
Abstract
Human cancers modeled in Genetically Engineered Mouse Models (GEMMs) can provide important mechanistic insights into the molecular basis of tumor development and enable testing of new intervention strategies. The inherent complexity of these models, with often multiple modified tumor suppressor genes and oncogenes, has hampered their use as preclinical models for validating cancer genes and drug targets. In our newly developed approach for the fast generation of tumor cohorts we have overcome this obstacle, as exemplified for three GEMMs; two lung cancer models and one mesothelioma model. Three elements are central for this system; (i) The efficient derivation of authentic Embryonic Stem Cells (ESCs) from established GEMMs, (ii) the routine introduction of transgenes of choice in these GEMM-ESCs by Flp recombinase-mediated integration and (iii) the direct use of the chimeric animals in tumor cohorts. By applying stringent quality controls, the GEMM-ESC approach proofs to be a reliable and effective method to speed up cancer gene assessment and target validation. As proof-of-principle, we demonstrate that MycL1 is a key driver gene in Small Cell Lung Cancer.
WEHI Research Division(s)
Stem Cells And Cancer
PubMed ID
24401838
Open Access at Publisher's Site
http://embomolmed.embopress.org/content/6/2/212
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-01-25 08:55:29
Last Modified: 2016-01-25 09:02:55
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