Format

Send to

Choose Destination
Hepatology. 2015 Mar;61(3):979-89. doi: 10.1002/hep.27539. Epub 2015 Jan 30.

Dysregulated serum response factor triggers formation of hepatocellular carcinoma.

Author information

1
Department for Molecular Biology, Interfaculty Institute of Cell Biology, Tuebingen University, Germany.

Erratum in

  • Hepatology. 2015 May;61(5):1772. Authenrieth, Stella E [corrected to Autenrieth, Stella E].

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-VP16iHep 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-VP16iHep 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.

CONCLUSION:

SRF-VP16iHep mHCC reveal convergent Ras/MAPK and Rho/actin signaling as a highly oncogenic driver mechanism for hepatocarcinogenesis. This suggests simultaneous inhibition of Ras/MAPK and Rho/actin signaling as a treatment strategy in hHCC therapy.

PMID:
25266280
PMCID:
PMC4365683
DOI:
10.1002/hep.27539
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center