|
Status |
Public on Sep 27, 2013 |
Title |
The Stress-Regulated Transcription Factor CHOP Promotes Hepatic Inflammatory Gene Expression, Fibrosis, and Oncogenesis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
|
Summary |
Viral hepatitis, obesity, and alcoholism all represent major risk factors for hepatocellular carcinoma (HCC). Although these conditions also lead to integrated stress response (ISR) or unfolded protein response (UPR) activation, the extent to which these stress pathways influence the pathogenesis of HCC has not been tested. Here we provide multiple lines of evidence demonstrating that the ISR-regulated transcription factor CHOP promotes liver cancer. We show that CHOP expression is upregulated in liver tumors in human HCC and two mouse models thereof. Chop-null mice are resistant to chemical hepatocarcinogenesis, and these mice exhibit attenuation of both apoptosis and cellular proliferation. Chop-null mice are also resistant to fibrosis, which is a key risk factor for HCC. Global gene expression profiling suggests that deletion of CHOP reduces the levels of basal inflammatory signaling in the liver. Our results are consistent with a model whereby CHOP contributes to hepatic carcinogenesis by promoting inflammation, fibrosis, cell death, and compensatory proliferation. They implicate CHOP as a common contributing factor in the development of HCC in a variety of chronic liver diseases.
|
|
|
Overall design |
24 samples were analyzed from 9 month old male C57BL/6J or backcrossed Chop-/- male mice, injected with either PBS or a single dose of 25 mg/kg diethylnitrosamine (DEN) at 15 d.o. Samples are either from whole liver or liver tumors.
|
|
|
Contributor(s) |
Rutkowski DT |
Citation(s) |
24367269 |
Submission date |
Sep 26, 2013 |
Last update date |
Aug 22, 2019 |
Contact name |
David Thomas Rutkowski |
E-mail(s) |
thomas-rutkowski@uiowa.edu
|
Organization name |
University of Iowa Carver College of Medicine
|
Department |
Anatomy and Cell Biology
|
Street address |
51 Newton Rd.
|
City |
Iowa City |
State/province |
IA |
ZIP/Postal code |
52242 |
Country |
USA |
|
|
Platforms (1) |
GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
Samples (24)
|
|
Relations |
BioProject |
PRJNA221566 |