Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors Conference Paper
| Authors: | Zender, L.; Xue, W.; Cordon-Cardo, C.; Hannon, G. J.; Lucito, R.; Powers, S.; Flemming, P.; Spector, M. S.; Lowe, S. W. |
| Title: | Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors |
| Conference Title: | 70th Cold Spring Harbor Symposium on Quantitative Biology |
| 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. © 2005 Cold Spring Harbor Laboratory Press. |
| Keywords: | controlled study; mutation; histopathology; liver cell carcinoma; nonhuman; conference paper; genetic analysis; animal cell; mouse; animals; mice; animal tissue; gene targeting; hepatocytes; gene expression; animal experiment; animal model; rna interference; mice, inbred c57bl; cancer mortality; gene transfer; genetic transduction; transduction, genetic; oncogenes; cancer invasion; oncogene; tumor suppressor gene; microarray analysis; oligonucleotide array sequence analysis; recombinant proteins; cancer stem cell; murinae; green fluorescent proteins; tumor model; genes, reporter; disease models, animal; ex vivo study; short hairpin rna; multipotent stem cells; genes, tumor suppressor; liver neoplasms, experimental; tumor stem cells; liver development |
| Journal Title | Cold Spring Harbor Symposia on Quantitative Biology |
| Volume: | 70 |
| Conference Dates: | 2005 Jun 1-6 |
| Conference Location: | Cold Spring Harbor, NY |
| ISBN: | 0091-7451 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2005-01-01 |
| Start Page: | 251 |
| End Page: | 261 |
| Language: | English |
| DOI: | 10.1101/sqb.2005.70.059 |
| PUBMED: | 16869761 |
| PROVIDER: | scopus |
| PMCID: | PMC4595853 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 22" - "Export Date: 24 October 2012" - "CODEN: CSHSA" - "Source: Scopus" |
