Page 151 - ebook HCC

EASL
GENEV
PROGRAMME AND ABSTRACTSAND ABSTRACTS
148
149
148 PROGRAMME GENEVA, SWITZERLANDA, SWITZERLAND EASL HCC SUMMITHCC SUMMIT 149
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
FEBRUAR
Poster Board Number B38 Poster Board Number B39
EXPRESSION OF TH1/TH2 CYTOKINES IN STUDY OF HNF4ALFA ROLE IN MOUSE LIVER
HEPATITIS B MEDIATED HEPATOCELLULAR
1
1
1
1
CARCINOMA IN PATIENTS FROM NORTH EAST Chiara Sartor , Cécile Godard , Angélique Gougelet , Christine Perret , Sabine Colnot 1
Inserm-Institut Cochin, Paris, France
1
INDIA
Corresponding author’s e-mail: chiara.sartor@inserm.fr
Manab Deka , Kangkana Kataki , Subhash Medhi , Sujoy Bose , Namrata Kumari ,
1
1
2
1
1
B B Borthakur , Anupam Sarma ,Amal C. Kataki 3 Introduction: Our laboratory is studying the role of beta-catenin signaling in the liver both
3
4
3
2
1 Department of Biological Science, Gauhati University, B Barooa Cancer Institute, in a physiological and a pathological status, through the use of transgenic mice models.
4 B Barua cancer institute, Guwahati, India In fact beta-catenin is able to establish and maintain the liver metabolic zonation, but also
is the cause of a percentage of liver cancers that are associated with a specific metabolic
Corresponding author’s e-mail: drmanabdeka@gmail.com phenotype.
Aims: We characterized the role of Hnf4α in vivo in beta-catenin-dependent zonation.
Introduction: Hepatitis B is one of the main causes of Hepatocellular Carcinoma (HCC) Knowing that beta-catenin is implicated in the emergence of liver tumors and that Hnf4α
worldwide. The infection by viruses lead to alter the Th1/Th2 cytokine profiles. The is depicted as a tumor suppressor gene, we also developed an in vivo project to looking
investigation of Th1/Th2 markers in case of HCC may be useful in better prognosis and further at its role in liver carcinogenesis.
management of the disease.
Methodology: We used an hepatospecific and Tamoxifen-inducible knock-out of either
BASIC POSTER ABSTRACTS Methodology: A total of 15 cases were included in the study which include HBV mediated previously developed and described by Gonzalez’s group. BASIC POSTER ABSTRACTS
Aims: This study was targeted to estimate Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10,
Hnf4α or Apc (Cre-loxP strategy). The Apc knock-out (Apc-ko) livers strongly over-activate
TNF-α and INF-γ) expression in HBV mediated HCC cases.
beta-catenin signaling, leading to tumor development. The Hnf4alfa-ko model has been
Hepatocellular carcinoma (HCC) N= 10 and Healthy control N=5. Cytokine profiles of
Results: In a first step, ChIP experiments performed in vivo (on hepatocytes activated or
the samples were analyzed using BD™ Cytometric Bead Array (CBA) Human Th1/Th2
inactivated for beta-catenin signaling) were analyzed combined to mRNA-Seq experiments.
Cytokine Kit II.
positive targets and showed a motif close to Hnf4 or PPAR Responsive Element (HRE)
Results: In all the samples IL6 showed highest expression. Irrespective of the etiology We identified the presence of a Wnt Responsive Element (WRE) upstream beta-catenin
upstream a pull of genes, 19% of that known as beta-catenin negative targets (Gougelet,
among HCC IL-6 showed highest concentration with an average of 1732.89 pg/µl±4310.63 Hepatology, in press).
followed by TNF-alpha with an average of 166.5pg/µl±484.844. The cytokine IL-2 didn’t Next, we made a comparison between the Hnf4α-ko livers and the Apc-ko ones. One week
show any expression. after inducible inactivation, the Hnf4α-ko livers have a modified zonation, as shown by
an extended staining of the Glutamine Synthetase (GS), a target of beta-catenin, and an
Conclusions: From the above study conducted it can be concluded that there is a increase of proliferation that is similar to the Apc-ko ones. Thus, Hnf4α and beta-catenin
significant increase in the expression of IL-6 in HBV mediated hepatocellular carcinoma signaling look antagonistic. But 20% of Hnf4α-ko livers also show a disorganization of the
compared to normal control where there is no expression and may be a prognostic marker . portal space, with a stenosis of the portal vein and an enlarged hepatic artery.
The small sample size is a limiting factor in this study which need further evaluation. The cohort of mice depleted in Hnf4α and let live until 9 months do not develop tumors.
However a subset of which present some GS-positive nodules and a disorganization in
portal and pericentral areas.
Conclusions: Hnf4α and beta-catenin signalings seem antagonistic for liver zonation.
Moreover, Hnf4α is not a tumor suppressor per se, and it rather takes part to the
maintenance of a normal liver zonal architecture.