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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  ;  Do Young Kim  ;  Sinhwa Baek  ;  Sook In Chung  ;  Jinsil Seong  ;  Kwang-Hyub Han  ;  Simon Weonsang Ro 
Citation
 PLOS ONE, Vol.8(3) : e59869, 2013 
Journal Title
 PLOS ONE 
Issue Date
2013
MeSH
Animals ; Carcinoma, Hepatocellular/metabolism* ; Disease Models, Animal* ; Gene Expression Regulation, Neoplastic* ; Hydrodynamics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology* ; Luciferases ; Luminescence ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; NIH 3T3 Cells ; Oncogenes ; Plasmids ; Time Factors ; Transfection ; Whole Body Imaging*
Keywords
Animals ; Carcinoma, Hepatocellular/metabolism* ; Disease Models, Animal* ; Gene Expression Regulation, Neoplastic* ; Hydrodynamics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology* ; Luciferases ; Luminescence ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; NIH 3T3 Cells ; Oncogenes ; Plasmids ; Time Factors ; Transfection ; Whole Body Imaging*
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.
Files in This Item:
T201301598.pdf Download
DOI
10.1371/journal.pone.0059869
Appears in Collections:
5. Research Institutes (연구소) > Liver Cirrhosis Clinical Research Center (간경변증임상연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Ro, Simon Weonsang(노원상) ORCID logo https://orcid.org/0000-0003-2187-3698
Baek, Sin Hwa(백신화)
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Chung, Sook In(정숙인) ORCID logo https://orcid.org/0000-0002-7915-9203
Ju, Hye Lim(주혜림)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86896
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