Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Murine hepatocellular carcinoma of AlbLTa/b transgenic mice and age matched C57BL/6 mice - 18 months old.

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: M HeikenwÃ¤lder

PROVIDER: E-GEOD-14467 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A lymphotoxin-driven pathway to hepatocellular carcinoma.

Haybaeck Johannes J Zeller Nicolas N Wolf Monika Julia MJ Weber Achim A Wagner Ulrich U Kurrer Michael Odo MO Bremer Juliane J Iezzi Giandomenica G Graf Rolf R Clavien Pierre-Alain PA Thimme Robert R Blum Hubert H Nedospasov Sergei A SA Zatloukal Kurt K Ramzan Muhammad M Ciesek Sandra S Pietschmann Thomas T Marche Patrice N PN Karin Michael M Kopf Manfred M Browning Jeffrey L JL Aguzzi Adriano A Heikenwalder Mathias M

Cancer cell 20091001 4

Hepatitis B and C viruses (HBV and HCV) cause chronic hepatitis and hepatocellular carcinoma (HCC) by poorly understood mechanisms. We show that cytokines lymphotoxin (LT) alpha and beta and their receptor (LTbetaR) are upregulated in HBV- or HCV-induced hepatitis and HCC. Liver-specific LTalphabeta expression in mice induces liver inflammation and HCC, causally linking hepatic LT overexpression to hepatitis and HCC. Development of HCC, composed in part of A6(+) oval cells, depends on lymphocyte ...[more]

PMID: 19800575

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Project description:Introduction: Hepatocellular carcinoma (HCC) is one of the most aggressive solid tumors and oncogenic pathways (e.g Akt, IGF signaling) are often activated in high proliferating HCC. Among several genetic alterations, epigenetic changes seem to be involved in the development and progression of HCC. DNA hypermethylation of promoter regions is almost always associated with transcriptional silencing and can lead to inactivation of tumor suppressor genes (TSG) in cancer cells. Aim: (1) To identify genes differently methylated in a subclass of HCC associated with proliferation and, (2) To correlate methylation changes with activation of molecular pathways. Methods: gDNA of 20 HCC, 8 cirrhotic and 8 normal liver samples was extracted and the methylation status was detected by the Illumina HumanMethylation27 BeadChip and immunohistochemistry of p-AKT, pIGF IR, p-S6 was analyzed. Results: Unsupervised clustering clearly classified normal livers, cirrhosis and HCC in 3 different groups. 961 genes were significantly hypermethylated in HCC compared to cirrhotic and 3942 genes showed hypermethylation in cirrhotic compared to normal liver tissue. 163 genes showed stepwise significant hypermethylation from normal to cirrhotic to HCC, including well described (p16, SOCS2, SFRP5, RBP1) and potential (SRD5A2, PCDH8, IGF-1R, UCHL1) TSGs, and the miR-10a. 133 genes were specifically hypermethylated in HCC. Among them the transcription factors GATA2, DLX1, and KLF14, all significantly inversely correlated to gene expression (p=0.003, p=0.03, and p=0.007, respectively). The methylation status of SOCS2 (p=0.025) and DLX1 (p=0.025) was significantly correlated to phosphorylation of IGFR1. Samples with RBP1 hypermethylation showed significantly higher AFP serum levels (p=0.018). Conclusion: Whole genome methylation analysis markedly classifies normal, cirrhotic and HCC samples. 8 TSGs play a key role in this stepwise progression of hypermethylation in the development of HCC and could be a promising point of action in anticancer therapy. Genomic DNA extracted from fresh frozen tissue specimens and cell lines was hybridized to genome-wide mthylation beadarray after bisulphite treatment. Keywords: DNA methylation, hepatocellular carcinoma, tissue, cell line

Dataset Information

Murine hepatocellular carcinoma of AlbLTa/b transgenic mice and age matched C57BL/6 mice - 18 months old.

Publications

A lymphotoxin-driven pathway to hepatocellular carcinoma.

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