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Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors.
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zender, L. Xue, W. Cordón-Cardo, C. Hannon, G. J. Lucito, R. Powers, S. Flemming, P. Spector, M. S. Lowe, S. W. |
| Description | Country affiliation: United States Author Affiliation: Zender L ( Cold Spring Harbor Laboratory, New York 11724, USA.) |
| 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. |
| File Format | HTM / HTML |
| ISSN | 00917451 |
| e-ISSN | 19434456 |
| Journal | Cold Spring Harbor Symposia on Quantitative Biology |
| Volume Number | 70 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2005-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biology Hepatocytes Pathology Liver Neoplasms, Experimental Genetics Multipotent Stem Cells Neoplastic Stem Cells Animals Disease Models, Animal Gene Targeting Genes, Reporter Genes, Tumor Suppressor Green Fluorescent Proteins In Vitro Techniques Mice Mice, Inbred C57bl Oligonucleotide Array Sequence Analysis Oncogenes Rna Interference Recombinant Proteins Transduction, Genetic Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Biochemistry Molecular Biology |
