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dc.contributor.authorHuijbers, IJ
dc.contributor.authorBin Ali, R
dc.contributor.authorPritchard, C
dc.contributor.authorCozijnsen, M
dc.contributor.authorKwon, M-C
dc.contributor.authorProost, N
dc.contributor.authorSong, J-Y
dc.contributor.authorde Vries, H
dc.contributor.authorBadhai, J
dc.contributor.authorSutherland, K
dc.contributor.authorKrimpenfort, P
dc.contributor.authorMichalak, EM
dc.contributor.authorJonkers, J
dc.contributor.authorBerns, A
dc.date.accessioned2020-12-18T03:21:34Z
dc.date.available2020-12-18T03:21:34Z
dc.date.issued2014-02
dc.identifierpii: emmm.201303297
dc.identifier.citationHuijbers, I. J., Bin Ali, R., Pritchard, C., Cozijnsen, M., Kwon, M. -C., Proost, N., Song, J. -Y., de Vries, H., Badhai, J., Sutherland, K., Krimpenfort, P., Michalak, E. M., Jonkers, J. & Berns, A. (2014). Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells.. EMBO Mol Med, 6 (2), pp.212-225. https://doi.org/10.1002/emmm.201303297.
dc.identifier.issn1757-4676
dc.identifier.urihttp://hdl.handle.net/11343/255735
dc.description.abstractHuman 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.
dc.languageeng
dc.publisherEMBO
dc.titleRapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells.
dc.typeJournal Article
dc.identifier.doi10.1002/emmm.201303297
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleEMBO Molecular Medicine
melbourne.source.volume6
melbourne.source.issue2
melbourne.source.pages212-225
dc.rights.licenseCC BY
melbourne.elementsid1300819
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927956
melbourne.contributor.authorSutherland, Kate
dc.identifier.eissn1757-4684
melbourne.accessrightsOpen Access


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