Page 121 - ebook HCC

PROGRAMME AND ABSTRACTSAND ABSTRACTS
GENEVA, SWITZERLANDA, SWITZERLAND
EASL HCC SUMMITHCC SUMMIT
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118 PROGRAMME GENEV EASL 119
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FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
FEBRUAR
Poster Board Number B17
UPREGULATION OF SMAD7 EXPRESSION
IN HEPATOCELLULAR CARCINOMA AS A
POTENTIAL MECHANISM FOR LOSS OF
CYTOSTATIC TGF-BETA EFFECTS

Teng Feng , Johanna Dzieran , Xing Gu , Hong L. Weng , Silke Marhenke , Although the above correlations were not verified when using normal tissue as reference,
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Thomas S. Weiß , Otto Kollmar , Heike Allgayer , Ulrich Lehmann , Smad7 overexpression indicated a better prognosis for HCC patients with tumors > 5cm
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Christoph Meyer , Steven Dooley , Nadja M. Meindl-Beinker 1 and without cirrhosis. In TGF-beta responsive Huh7 cells, Smad7 overexpression inhibited
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1 Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, TGF-beta induced proliferation control. Hepatocyte specific Smad7 overexpression
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Heidelberg University, Mannheim, Germany, Department of Laboratory Medicine, increased proliferative activity in FAH knock out mice in the early phase of liver damage.
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, Knock down of intrinsically high Smad7 levels in TGF-beta insensitive FLC-4 cells using
China, Department of Gastroenterology, Hepatology and Endocrinology, Medical School RNAi partially restored the cytostatic response of FLC-4 to TGF-beta.
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Hannover, Hannover, Department of Pediatrics and Juvenile Medicine, Center for Liver
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Cell Research, University of Regensburg Hospital, Regensburg, Department of General, We excluded differential methylation of a GC rich Smad7 promoter region as mechanism
Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, for Smad7 upregulation in HCC. Instead we found involvement of the YB1 transcription
6 Department of Experimental Surgery, Medical Faculty Mannheim, Heidelberg University, factor. Knock down of YB1 reduced Smad7 expression in Huh7 and FLC-4 cells and
Mannheim, Institute of Pathology, Medical School Hannover, Hannover, Germany overexpression of YB1 was found in 27 out of 28 patients with high Smad7 levels.
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Immunofluorescence showed co-staining of Smad7 and YB1 in HCC samples of patients.
BASIC POSTER ABSTRACTS Introduction: TGF-beta is critical in tumorigenesis of HCC with context-dependent Sorafenib. BASIC POSTER ABSTRACTS
Finally, increased Smad7 expression sensitizes Huh7 cells for anti-proliferative effects of
Corresponding author’s e-mail: Nadja.Meindl-Beinker@medma.uni-heidelberg.de
Conclusions: Our results suggest that Smad7 upregulation may represent one
effects. It is accepted that the TGF-β signaling inhibitor Smad7may also act as tumorigenic
mechanism for loss of cytostatic TGF-β effects in early hepatocellular carcinoma. There
mediator in HCC, while its precise role remains unclear.
disease prognosis and Sorafenib treatment.
Aims: We investigated the expression profile of Smad7 in human HCC and its correlation is evidence that Smad7 expression can be a biomarker in subgroups of HCC patients for
to clinicopathological parameters. We studied regulatory mechanisms of Smad7 induction,
its functional role in HCC and its impact on Sorafenib sensitivity.
Methodology: Smad7 expression in 140 paired human HCC patient samples was analyzed
by q-PCR and correlated to e.g. HCC etiology and survival. The role of Smad7 expression
levels in HCC was studied in HCC cell lines and FAH knockout mice. Methylation analysis
of the Smad7 promotor as well as overexpression and knockdown of transcription factor
YB1 were used to analyze Smad7 expression regulation.
Results: In 58.5% of 140 HCC samples we found Smad7 upregulation compared to
adjacent non-tumor tissue of the same patient correlating with HBV infection, tumor size
and grade. Smad7 was also upregulated in HCC tissue vs `normal´ liver tissue from non-
HCC patients.