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Investigation of Oncogenic Cooperation in Simple Liver-Specific Transgenic Mouse Models Using Noninvasive In Vivo Imaging

Authors
 Hye-Lim Ju ; Sang Hoon Ahn ; Simon Weonsang Ro ; Kwang-Hyub Han ; Jinsil Seong ; Sook In Chung ; Sinhwa Baek ; Do Young Kim 
Citation
 PLoS One, Vol.8(3) : e59869, 2013 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2013
Abstract
iver cancer is a complex multistep process requiring genetic alterations in multiple proto-oncogenes and tumor suppressor genes. Although hundreds of genes are known to play roles in hepatocarcinogenesis, oncogenic collaboration among these genes is still largely unknown. Here, we report a simple methodology by which oncogenic cooperation between cancer-related genes can be efficiently investigated in the liver. We developed various non-germline transgenic mouse models using hydrodynamics-based transfection which express HrasG12V, SmoM2, and a short-hairpin RNA down-regulating p53 (shp53) individually or in combination in the liver. In this transgenic system, firefly luciferase was co-expressed with the oncogenes as a reporter, allowing tumor growth in the liver to be monitored over time without an invasive procedure. Very strong bioluminescence imaging (BLI) signals were observed at 4 weeks post-hydrodynamic injection (PHI) in mice co-expressing HrasG12V and shp53, while only background signals were detected in other double or single transgenic groups until 30 weeks PHI. Consistent with the BLI data, tumors were observed in the HrasG12V plus shp53 group at 4 weeks PHI, while other transgenic groups failed to exhibit a hyperplastic nodule at 30 weeks PHI. In the HrasG12V plus shp53 transgenic group, BLI signals were well-correlated with actual tumor growth in the liver, confirming the versatility of BLI-based monitoring of tumor growth in this organ. The methodology described here is expected to accelerate and facilitate in vivo studies of the hepatocarcinogenic potential of cancer-related genes by means of oncogenic cooperation.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86896
DOI
10.1371/journal.pone.0059869
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Liver Cirrhosis Clinical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Radiation Oncology
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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