Alpha-fetoprotein-thymidine kinase-luciferase knockin mice: a novel model for dual modality longitudinal imaging of tumorigenesis in liver.
Alpha-fetoprotein-thymidine kinase-luciferase knockin mice: a novel model for dual modality longitudinal imaging of tumorigenesis in liver.
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DOI：
10.1016/j.jhep.2010.10.020
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发表时间：
2011-07
影响因子：
25.7
通讯作者：
Wang, Bingcheng
中科院分区：
文献类型：
--
作者：
Lu, Xincheng;Guo, Hong;Molter, Joseph;Miao, Hui;Gerber, Lizabeth;Hu, Yiduo;Barnes, Ellen L.;Vogel, Hannes;Lee, Zhenghong;Luo, Guangbin;Wang, Bingcheng
关键词：
Hepatocellular carcinoma (HCC) is frequently a lethal disease and one of the few malignancies that are still increasing in incidences around the world. Better animal models are highly desired to investigate the molecular basis of HCC and to develop novel therapeutic strategies. Alpha-fetoprotein (Afp) gene is expressed in fetal liver, silenced soon after birth, and highly re-expressed in hepatocellular carcinomas (HCC). We aimed to take advantage of the dramatic re-expression of Afp gene in HCC to develop a hepatocarcinogenesis reporter (HCR) mouse model for dual-modality, longitudinal in vivo imaging of liver tumor development and progression. Knockin mice were established by placing a thymidine kinase (tk) - luciferase (luc) reporter gene cassette under the transcriptional control of the endogenous Afp promoter. DEN, a liver carcinogen, was used to induce liver tumors, which was monitored by both luc-based bioluminescent (BL) and tk-based positron emission tomography (PET) imaging. The expression profile of luc was identical to that of endogenous Afp gene during development. As early as two month after exposure to DEN, BLI revealed multifocal signals in the liver, long before the appearance of histologically apparent neoplastic lesions. By six months, BL and PET dual imaging showed strong signals in malignant HCC. By serendipity, strong BL signal was also detected in adult testes, a previously unknown site of Afp expression. The HCR model enables longitudinal monitoring of liver tumor development and progression, providing a powerful tool in developing chemoprevention and therapeutic strategies for HCC.
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