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| Status |
Public on Feb 28, 2014 |
| Title |
Gene expression profile of liver tissue in carbon tetrachloride (CCl4)-treated mouse treated with erlotinib |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Gene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated mouse and the effect of erlotinib
Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. Given the lack of successful treatment options, chemoprevention in high-risk patients has been proposed as an alternative strategy. Mounting evidence supports a role for epidermal growth factor (EGF) during chronic liver disease and hepatocellular transformation. We address the hypothesis that blocking the EGF-EGF receptor (EGFR) pathway may be an effective strategy for inhibiting fibrogenesis and hepatocarcinogenesis. A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the effects of erlotinib on underlying chronic liver disease and HCC formation. The DEN-induced rat model closely resembles disease progression in humans both pathologically and molecularly. Erlotinib significantly prevented the development of HCC tumor nodules in a dose-dependent fashion. Further, erlotinib inhibited the activation of hepatic stellate cells and prevented fibrogenesis. Erlotinib also reduced hepatotoxicity and improved liver function. Finally, a gene expression signature predictive of poor survival in human cirrhosis patients was reversed in response to erlotinib. Our data demonstrate for the first time that EGFR inhibition prevents liver fibrogenesis. Further, our results suggest that erlotinib is a potentially effective HCC chemoprevention strategy through inhibition of cirrhosis progression which can be monitored at the molecular level.
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| Overall design |
Animals received humane care according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals” of the National Academy of Sciences. All animals were maintained in accordance with the institutional guidelines of the Massachusetts General Hospital Subcommittee on Research Animal Care. Strain A/J male mice (Jackson Laboratory, Bar Harbor, ME) were treated three times a week for 18 weeks with either 0.1cc of a 40 percent solution of CCl4 (Sigma) in olive oil or with vehicle control by oral gavage. Mice were sacrificed at 19 weeks after a one-week washout to eliminate acute effects of CCl4. The liver was sectioned and fixed in phosphate-buffered 10% formaldehyde for histological analysis. The remaining portions of the liver were collected in RNase-free tubes and snap-frozen in liquid nitrogen. Frozen tissues were stored at -80°C until use.
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| Contributor(s) |
Fuchs BC, Hoshida Y, Fujii T, Yamada S, Lauwers GY, McGinn CM, Wei L, Kuroda T, Lanuti M, Gupta S, Crenshaw A, Onofrio R, Taylor B, Winckler W, Golub TR, Tanabe KK |
| Citation(s) |
24677197 |
| Submission date |
Mar 02, 2011 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Yujin Hoshida |
| E-mail(s) |
Yujin.Hoshida@UTSouthwestern.edu
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| Organization name |
University of Texas Southwestern Medical Center
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| Street address |
5323 Harry Hines Blvd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE27641 |
EGFR inhibition prevents liver cirrhosis and hepatocellular carcinoma |
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| Relations |
| BioProject |
PRJNA141763 |
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