Development of a conditional liver tumor model by mifepristone-inducible Cre recombination to control oncogenic kras(V12) expression in transgenic zebrafish Public Deposited

http://ir.library.oregonstate.edu/concern/articles/6w924d435

This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at:  http://www.nature.com/articles/srep19559

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  • Development of a conditional liver tumor model by mifepristone-inducible Cre recombination to control oncogenic kras[superscript]V12 expression in transgenic zebrafish
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  • Here we report a new transgenic expression system by combination of liver-specific expression, mifepristone induction and Cre-loxP recombination to conditionally control the expression of oncogenic kras[superscript]V12. This transgenic system allowed expression of kras[superscript]V12 specifically in the liver by a brief exposure of mifepristone to induce permanent genomic recombination mediated by the Cre-loxP system. We found that liver tumors were generally induced from multiple foci due to incomplete Cre-loxP recombination, thus mimicking naturally occurring human tumors resulting from one or a few mutated cells and clonal proliferation to form nodules. Similar to our earlier studies by both constitutive and inducible expression of the kras[superscript]V12 oncogene, hepatocellular carcinoma (HCC) is the main type of liver tumor induced by kras[superscript]V12 expression. Moreover, mixed tumors with hepatocellular adenoma and hepatoblastoma (HB) were also frequently observed. Molecular analyses also indicated similar increase of phosphorylated ERK1/2 in all types of liver tumors, but nuclear localization of β–catenin, a sign of malignant transformation, was found only in HCC and HB. Taken together, our new transgenic system reported in this study allows transgenic kras[superscript]V12 expression specifically in the zebrafish liver only by a brief exposure of mifepristone to induce permanent genomic recombination mediated by the Cre-loxP system.
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  • Nguyen, A. T., Koh, V., Spitsbergen, J. M., & Gong, Z. (2016). Development of a conditional liver tumor model by mifepristone-inducible Cre recombination to control oncogenic krasV12 expression in transgenic zebrafish. Scientific Reports, 6, 19559. doi:10.1038/srep19559
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  • description.provenance : Made available in DSpace on 2016-02-19T16:00:58Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) NguyenAnhMicrobioDevelopmentConditionalLiver.pdf: 2058398 bytes, checksum: ef0b1eb9009747439ffd9920991d6dd6 (MD5) NguyenAnhMicrobioDevelopmentConditionalLiver(Supplement).pdf: 23883 bytes, checksum: 2134725a67f908fc0cc23d32576714d3 (MD5) Previous issue date: 2016-01-21
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  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2016-02-19T16:00:29Z No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) NguyenAnhMicrobioDevelopmentConditionalLiver.pdf: 2058398 bytes, checksum: ef0b1eb9009747439ffd9920991d6dd6 (MD5) NguyenAnhMicrobioDevelopmentConditionalLiver(Supplement).pdf: 23883 bytes, checksum: 2134725a67f908fc0cc23d32576714d3 (MD5)

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