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NguyenAnhMicrobioDevelopmentConditionalLiver(Supplement).pdf

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https://ir.library.oregonstate.edu/concern/articles/xw42n962j

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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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file details NguyenAnhMicrobioDevelopmentConditionalLiver_Supplement_.pdf 2017-07-26 Público Descargar