Hepatocellular carcinoma (HCC) in FEAT transgenic mouse
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE18403 | GEO | 2009/10/15
SECONDARY ACCESSION(S): PRJNA118249
REPOSITORIES: GEO
Similar Datasets
Project description:Hepatocellular carcinoma (HCC) in FEAT transgenic mouse
| PRJNA118249 | ENA
Project description:Hepatocellular carcinoma (HCC) is the most common liver cancer and a highly malignant tumor. The frequent activation of Ras signaling pathway and the male prevalence are the distinct characteristics of HCC though the underlying mechanisms remain elucidated. By exploring a mouse model of HCC induced by hepatocyte-specific expression of the Hras12V oncogene and showed significant male prevalence in hepatic tumorigenesis, we performed a high-throughput comparative proteomic analysis based on tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the protein samples from hepatic tumor tissues (T) and peri-tumor tissues (P) of transgenic males and females and the corresponding normal liver tissues (W) of non-transgenic males and females. In total, 5733 proteins were confidently identified, of which 5193 proteins were quantified. Finally, 1344 differentially expressed proteins (DEPs) (quantified in all examined samples; 1.5 ≤ quantitative ratios ≤ 0.67; p ≤ 0.05) were selected for further analysis. Vertical comparison within W, P, T of males and females, respectively, showed that the numbers of DEPs in males were much higher than females. Bioinformatics analyses showed the common and unique cluster enriched items between sexes which indicates the common and gender disparity pathways towards HCC. Further expression change pattern analysis revealed HCC positive/negative-related and Ras oncogene positive/negative-related DEPs. Horizontal comparison between males and females showed that Ras oncogene gradually and significantly reduced the responses to sex hormones from hepatocytes to hepatoma cells and therefore shrunk their gender disparity, which may contribute to the cause of the loss of HCC clinical responses to the therapeutic approaches targeting sex hormone pathways. Additionally, FABP5 was found to be a more sensitive biomarker for clinical diagnose and prognosis prediction of HCC patients comparing to AFP. In conclusion, the present study firstly provided a comprehensive proteome profiles and novel insights in male bias hepatic tumorigenesis induced by H-ras12V oncogene.
2021-09-08 | PXD012410 | Pride
Project description:Astrocyte elevated gene-1 (AEG-1) as a positive inducer of hepatocellular carcinoma (HCC). Transgenic mice with hepatocyte-specific expression of AEG-1 were challenged with N-nitrosodiethylamine (DEN) and developed multinodular HCC with steatotic features. Thus, we have identified the follwoing AEG-1 functions: induction of steatosis, inhibition of senescence and activation of coagulation pathway to augment an aggressive hepatocarcinogenic phenotype. Transgenic Mice liver tumors compared against WT mice liver tumors.
2012-07-24 | E-GEOD-34669 | biostudies-arrayexpress
Project description:aCGH analysis of murine transgenic liver tissues affected with HCC, hybridized with age (18 months) and sex matched C57BL/6 mice. Moreover, 18months old C57BL/6 livers were hybridized with independent 18 months old C57BL/6 livers for control. Keywords: Array comparative genomic hybridization analysis (aCGH). Independent HCC of AlbLTab mice were hybridized with independent C57BL/6 mice.
2010-05-15 | E-GEOD-14467 | biostudies-arrayexpress
Project description:Liver cirrhosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet the mechanisms by which cirrhosis predisposes patients to tumorigenesis are not well understood. Transgenic mice expressing platelet-derived growth factor C (Pdgf-c) under the control of the albumin promoter provide a unique animal model that mimics the step-wise disease progression in humans from fibrosis to HCC. The livers of Pdgf-c Tg mice show evidence of liver injury, including inflammation, proliferation, fibrosis and steatosis, and as the mice age, angiogenesis and dysplasia. Eighty-five percent of these mice develop HCC spontaneously, and have reduced survival that is related to their liver pathology. Through measurement of protein, RNA, and histological markers, we provide evidence to support the hypothesis that changes in liver stromal cells play an essential role in tumorigenesis in this model. A paracrine signaling model is proposed where ectopic expression of Pdgf-c in hepatocytes results in activation of hepatic stellate cells, which subsequently activates endothelial and Kupffer cells. Activation of these non-parenchymal cells promotes the release of hepatocyte growth factors that, together with changes in extracellular matrix, lead to the formation of HCC. Pdgf-c Tg mice provide a useful pre-clinical model in which to test novel drugs for chronic liver disease and HCC that focus on blocking the processes that alter the liver's fibrotic microenvironment. Two strains of mice, C57BL/6 and C57/BL6 Pdgf-c transgenic, were analyzed to see if liver stromal cells play an essential role in tumorigenesis.
2014-05-12 | E-GEOD-38199 | biostudies-arrayexpress
Project description: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. 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.
2013-09-27 | E-GEOD-51188 | biostudies-arrayexpress
Project description:aCGH analysis of murine transgenic liver tissues affected with HCC, hybridized with age (12 months) and sex matched alb cre mice. Keywords: Array comparative genomic hybridization analysis (aCGH). Independent HCC of MCL1-/- mice were hybridized with pooled wt mice. Mclâ1flox/flox mice (C57BL/6 background) were obtained from the Dana Farber Cancer Institute, Boston, USA (Opferman JT et al., Nature 2003) and bred to heterozygous Albumin-Cre mice (C57BL/6 background) which led to hepatocyte-specific deletion of Mcl-1. The mice develop severe chronic liver damage (Vick B et al., Hepatology, 2009).
2010-05-16 | E-GEOD-16580 | biostudies-arrayexpress
Project description:61 human HCCs were analyzed for genome-wide gene expression. Samples were collected at two sites in Germany, Heidelberg (HD) and Hannover (N). The Heidelberg Collection include 40 independent HCC: 19 liver resections and 17 explant liver specimen (4 not determined); median age at surgery was 57 years (range, 16-78), and the male/female ratio was 3:1. All diagnoses were confirmed by histological reevaluation, and use of the samples was approved by the local ethics committee. From 3 patients, two HCC nodules were included that previously showed different aCGH, indicating independent tumor development (tagged by _2). The underlying etiologies were HBV (n=8), HCV (n=9), alcohol (n=14), cryptogenic (n=11), genetic hemochromatosis (n=3), and Alpha-1 antitrypsin deficiency (n=2). The Hannover Collection include 21 HCC (HCC-Grad: G1-G3). Technical replicates were tagged with _B or _C differential genes expression in HCC liver (n=61) compared to control group (cell lines, n=3; normal liver tissue(NL), n=7). Technical replicates are indicated by _2.
2013-09-05 | E-GEOD-50579 | biostudies-arrayexpress
Project description:Chronic inflammation is a common underlying condition associated with tumor development, accounting for approximately 20% of human cancers. This association is especially apparent in Hepatocellular carcinoma (HCC), which often develops on the background of chronic hepatitis and hepatic fibrosis, slowly unfolding on a background of chronic inflammation. HCC is one of the most common tumors worldwide, exhibiting a very poor prognosis and high mortality rate with limited available therapeutic tools. The etiology of liver cancer is well known, however there is still a lack of precise knowledge about pathogenesis of HCC. IL-6 have been shown to be of importance for liver protection and prevention of liver injury in animal models of acute sclerosing cholangitis and correlate with increased HCC in human patients. Using a murine model of chronic cholangitis based on the ablation of the Mdr2 gene, this study has examined the role of IL-6 signaling in chronic hepatitis and in the subsequent development of liver cancer. The main observations of this study are that IL-6 signaling in male Mdr2-KO mice protects from the development of liver injury and fibrosis, but simultaneously promotes tumor initiation. Thus, IL-6 deficiency in male Mdr2-KO mice dissociates the tight correlation between liver fibrosis and the development of inflammation-associated HCC. To reveal the affected molecular pathways that lead to increased cholestasis and bile acid–induced liver injury, but reduced tumorigenesis in the male IL-6 deficient Mdr2-KO/IL6-KO mice, we performed gene array analysis and identified distinct classes of differentially-expressed genes in these mice. We performed genome-scale gene expression profiling by Affymetrix analysis on tumor-free livers samples from Mdr2-KO, Mdr2-KO/IL6-KO, and wild type C57BL/6 mice at the age of 14 months.
2015-05-01 | E-GEOD-37468 | biostudies-arrayexpress
Project description:Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5+/- mice develop HCC in a male-biased manner. Here we show that NCOA5 expression was reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, was lower in female HCCs. Tip30 heterozygous deletion did not change HCC incidence in Ncoa5+/- male mice but dramatically increased HCC incidence in Ncoa5+/- female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperated with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hindered HCC development in female mice. Furthermore, HCN3 amplification and overexpression occurred in human HCCs and correlated with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver.
2023-08-29 | GSE228531 | GEO