Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors

Zender, L., Xue, W., Cordon-Cardo, C., Hannon, G. J., Lucito, R., Powers, S., Flemming, P., Spector, M. S., Lowe, S. W. (2005) Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors. Cold Spring Harb Symp Quant Biol, 70 (1). pp. 251-261. ISSN 1943-4456 (Electronic) 0091-7451 (Linking)

DOI: 10.1101/sqb.2005.70.059


Hepatocellular carcinoma is a chemoresistant cancer and a leading cause of cancer mortality; however, the molecular mechanisms responsible for the aggressive nature of this disease are poorly understood. In this study, we developed a new liver cancer mouse model that is based on the ex vivo genetic manipulation of embryonic liver progenitor cells (hepatoblasts). After retroviral gene transfer of oncogenes or short hairpin RNAs targeting tumor suppressor genes, genetically altered liver progenitor cells are seeded into the liver of otherwise normal recipient mice. We show that histopathology of the engineered liver carcinomas reveals features of the human disease. Furthermore, representational oligonucleotide microarray analysis (ROMA) of murine liver tumors initiated by two defined genetic hits revealed spontaneously acquired genetic alterations that are characteristic for human hepatocellular carcinoma. This model provides a powerful platform for applications like cancer gene discovery or high-throughput preclinical drug testing.

Item Type: Paper
Uncontrolled Keywords: Animals Disease Models Animal Female Gene Targeting Genes Reporter Genes Tumor Suppressor Green Fluorescent Proteins genetics Hepatocytes pathology Humans Liver Neoplasms Experimental genetics pathology Mice Mice Inbred C57BL Multipotent Stem Cells pathology Oligonucleotide Array Sequence Analysis Oncogenes RNA Interference Recombinant Proteins genetics Transduction Genetic Tumor Stem Cells pathology
Subjects: diseases & disorders > cancer > cancer types > liver cancer
organism description > model organism
organism description > animal > mammal > rodent > mouse
therapies > stem cells
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Lowe lab
CSHL labs > Lucito lab
CSHL labs > Powers lab
Depositing User: Brian Soldo
Date: 2005
Date Deposited: 28 Mar 2012 19:44
Last Modified: 01 Mar 2013 21:02
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