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PMID: 16869761 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors.

Cold Spring Harbor symposia on quantitative biology ·Vol. 70 ·2005-00-00 ·Pages 251-61

Zender L, Xue W, Cordón-Cardo C, Hannon GJ, Lucito R, Powers S, Flemming P, Spector MS, Lowe SW

Abstract

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.

MeSH Terms
Animals Disease Models, Animal Female Gene Targeting Genes, Reporter Genes, Tumor Suppressor Green Fluorescent Proteins/genetics Hepatocytes/pathology Humans In Vitro Techniques Liver Neoplasms, Experimental/genetics,pathology Mice Mice, Inbred C57BL Multipotent Stem Cells/pathology Neoplastic Stem Cells/pathology Oligonucleotide Array Sequence Analysis Oncogenes RNA Interference Recombinant Proteins/genetics Transduction, Genetic
Chemicals
Recombinant Proteins Green Fluorescent Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zender L
Cold Spring Harbor Laboratory, New York 11724, USA.
Xue W
Cordón-Cardo C
Hannon G J
Lucito R
Powers S
Flemming P
Spector M S
Lowe S W
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Article Info
Journal
Cold Spring Harbor symposia on quantitative biology
Abbr.
Cold Spring Harb Symp Quant Biol
ISSN
0091-7451
DOI
10.1101/sqb.2005.70.059
Published
2005-00-00
Pages
251-61
Language
English
Region
United States
NLM ID
1256107
PMCID
PMC4595853
Subset
IM
Grants
NCI NIH HHS · CA13106 · United States
NCI NIH HHS · P30 CA008748 · United States
NCI NIH HHS · P01 CA087497 · United States
NCI NIH HHS · U01 CA105388 · United States
NCI NIH HHS · P01 CA013106 · United States
NCI NIH HHS · CA105388 · United States
NCI NIH HHS · CA87497 · United States
External Links
PubMed source DOI: 10.1101/sqb.2005.70.059 PMC Full Text
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