Dysregulated serum response factor triggers formation of hepatocellular carcinoma.

Ohrnberger, Stefan; Thavamani, Abhishek; Braeuning, Albert; Lipka, Daniel B; Kirilov, Milen; Geffers, Robert; Authenrieth, Stella E; Römer, Michael; Zell, Andreas; Bonin, Michael; Schwarz, Michael; Schütz, Günther; Schirmacher, Peter; Plass, Christoph; Longerich, Thomas; Nordheim, Alfred

dc.contributor.author	Ohrnberger, Stefan
dc.contributor.author	Thavamani, Abhishek
dc.contributor.author	Braeuning, Albert
dc.contributor.author	Lipka, Daniel B
dc.contributor.author	Kirilov, Milen
dc.contributor.author	Geffers, Robert
dc.contributor.author	Authenrieth, Stella E
dc.contributor.author	Römer, Michael
dc.contributor.author	Zell, Andreas
dc.contributor.author	Bonin, Michael
dc.contributor.author	Schwarz, Michael
dc.contributor.author	Schütz, Günther
dc.contributor.author	Schirmacher, Peter
dc.contributor.author	Plass, Christoph
dc.contributor.author	Longerich, Thomas
dc.contributor.author	Nordheim, Alfred
dc.date.accessioned	2015-03-23T13:31:18Z	en
dc.date.available	2015-03-23T13:31:18Z	en
dc.date.issued	2015-03	en
dc.identifier.citation	Dysregulated serum response factor triggers formation of hepatocellular carcinoma. 2015, 61 (3):979-89 Hepatology	en
dc.identifier.issn	1527-3350	en
dc.identifier.pmid	25266280	en
dc.identifier.doi	10.1002/hep.27539	en
dc.identifier.uri	http://hdl.handle.net/10033/346988	en
dc.description.abstract	The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen-activated protein kinase) and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF-VP16(iHep) mice, which conditionally express constitutively active SRF-VP16 in hepatocytes, thereby controlling subsets of both Ras/MAPK- and Rho/actin-stimulated target genes. All SRF-VP16(iHep) mice develop hyperproliferative liver nodules that progresses to lethal HCC. Some murine (m)HCCs acquire Ctnnb1 mutations equivalent to those in human (h)HCC. The resulting transcript signatures mirror those of a distinct subgroup of hHCCs, with shared activation of oncofetal genes including Igf2, correlating with CpG hypomethylation at the imprinted Igf2/H19 locus.
dc.language.iso	en	en
dc.title	Dysregulated serum response factor triggers formation of hepatocellular carcinoma.	en
dc.type	Article	en
dc.contributor.department	Helmholtz Centre for infection research, Inhoffenstr. 7., 38124 Braunschweig, Germany.	en
dc.identifier.journal	Hepatology (Baltimore, Md.)	en
refterms.dateFOA	2018-06-12T21:27:03Z
html.description.abstract	The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen-activated protein kinase) and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF-VP16(iHep) mice, which conditionally express constitutively active SRF-VP16 in hepatocytes, thereby controlling subsets of both Ras/MAPK- and Rho/actin-stimulated target genes. All SRF-VP16(iHep) mice develop hyperproliferative liver nodules that progresses to lethal HCC. Some murine (m)HCCs acquire Ctnnb1 mutations equivalent to those in human (h)HCC. The resulting transcript signatures mirror those of a distinct subgroup of hHCCs, with shared activation of oncofetal genes including Igf2, correlating with CpG hypomethylation at the imprinted Igf2/H19 locus.