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Type of publication: Journal Article
Type of document: Full Paper

Year: 2019

Authors: Kaltenecker, D; Themanns, M; Mueller, KM; Spirk, K; Golob-Schwarzl, N; Friedbichler, K; Kenner, L; Haybaeck, J; Moriggl, R

Title: STAT5 deficiency in hepatocytes reduces diethylnitrosamine-induced liver tumorigenesis in mice.

Source: Cytokine. 2019; 124:154573

Authors Vetmeduni Vienna:

Kaltenecker Doris
Kenner Lukas
Moriggl Richard
Müller Kristina
Spirk Katrin
Themanns Madeleine

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals
Institute of Animal Breeding and Genetics, Unit for Functional Cancer Genomics

Chronic liver diseases and the development of hepatocellular carcinoma are closely linked and pose a major medical challenge as treatment options are limited. Animal studies have shown that genetic deletion of the signal transducer and activator of transcription (STAT) 5 in liver is associated with higher susceptibility to fatty liver disease, fibrosis and cancer, indicating a protective role of hepatic STAT5 in mouse models of chronic liver disease. To investigate the role of STAT5 in the etiology of liver cancer in more detail, we applied the chemical carcinogen diethylnitrosamine (DEN) to mice harboring a hepatocyte-specific deletion of Stat5 (S5KO). At 8 months after DEN injections, tumor formation in S5KO was significantly reduced. This was associated with diminished tumor frequency and less aggressive liver cancer progression. Apoptosis and inflammation markers were not changed in S5KO livers suggesting that the reduced tumor burden was not due to impaired inflammatory response. Despite reduced mRNA expression of the DEN bio-activator cytochrome P450 2e1 (Cyp2e1) in S5KO livers, protein levels were similar. Yet, delayed tumor formation in S5KO mice coincided with decreased activation of c-Jun N-terminal Kinase (JNK). Taken together, while STAT5 has a protective role in fatty liver-associated liver cancer, it exerts oncogenic functions in DEN-induced liver cancer.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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