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Series GSE27638 Query DataSets for GSE27638
Status Public on Feb 28, 2014
Title Gene expression profile of hepatocellular carcinoma in low-dose, repeated diethylnitrosamine (DEN)-treated rat treated with erlotinib
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary Gene-expression profiles of rat hepatocellular carcinoma induced by diethylnitrosamine (DEN) 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.
 
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. Male Wistar rats received weekly IP injections of diethylnitrosamine (DEN) at 50 mg/kg, 100mg/kg, or vehicle control (PBS) for 18 weeks. A subset of rats received either daily (5X a week) IP injections of 2 mg/kg erlotinib or vehicle control during weeks 13 - 18. In a separate study, the erlotinib dose was lowered to 0.5 mg/kg. The vehicle groups from the two studies were not significantly different so they were combined together for analysis. Rats were weighed at the end of each week. Animals were sacrificed at 9, 13 and 19 weeks after a one-week washout period to eliminate acute effects of DEN. At the time of sacrifice, the non-tumor liver tissues were collected in RNase-free tubes and snap-frozen in liquid nitrogen. Frozen tissues were stored at -80°C until RNA extraction.
 
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 Jul 29, 2014
Contact name Yujin Hoshida
E-mail(s) Yujin.Hoshida@UTSouthwestern.edu
Organization name University of Texas Southwestern Medical Center
Street address 5323 Harry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75390
Country USA
 
Platforms (1)
GPL6101 Illumina ratRef-12 v1.0 expression beadchip
Samples (6)
GSM684865 Tumor_18w_erlotinib2_DEN_126
GSM684866 Tumor_18w_erlotinib2_DEN_127
GSM684867 Tumor_18w_erlotinib2_DEN_138
This SubSeries is part of SuperSeries:
GSE27641 EGFR inhibition prevents liver cirrhosis and hepatocellular carcinoma
Relations
BioProject PRJNA141761

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE27638_RAW.tar 2.8 Mb (http)(custom) TAR
GSE27638_non-normalized.txt.gz 613.7 Kb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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