Skip to main content

Hepatocyte Wnts Are Dispensable During Diethylnitrosamine and Carbon Tetrachloride-Induced Injury and Hepatocellular Cancer

The full text article is temporarily unavailable.

We apologise for the inconvenience. Please try again later.

Activation of the Wnt/β-catenin signaling is reported in large subsets of hepatocellular carcinoma (HCC). Upregulation of Wnt genes is one contributing mechanism. In the current study, we sought to address the role of hepatocyte-derived Wnts in a model of hepatic injury, fibrosis, and carcinogenesis. We subjected hepatocyte-specific Wntless knockout mice (HP-KO), unable to secrete Wnts from hepatocytes, and littermate controls (HP-CON) to diethylnitrosamine and carbon tetrachloride (DEN/CCl4) and harvested at 3, 5, and 6 months for histological and molecular analysis. Analysis at 5 months displayed increased hepatic expression of several Wnts and upregulation of some, but not all, β-catenin targets, without mutations in Ctnnb1. At 5 months, HP-CON and HP-KO had comparable tumor burden and injury; however, HP-KO uniquely showed small CK19+ foci within tumors. At 6 months, both groups were moribund with comparable tumor burden and CK19 positivity. While HCC histology was indistinguishable between the groups, HP-KO exhibited increased active β-catenin and decreased c-Myc, Brd4, E-cadherin, and others. Hepatic injury, inflammation, and fibrosis were also indistinguishable at 3 months between both groups. Thus, lack of Wnt secretion from hepatocytes did not affect overall injury, fibrosis, or HCC burden, although there were protein expression differences in the tumors occurring in the two groups.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: Carbon tetrachloride; Diethylnitrosamine; Hepatocellular carcinoma; Wnt; β-Catenin

Document Type: Research Article

Affiliations: Department of Pathology, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Publication date: 22 August 2018

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more