Feng, T. and Dzieran, J. and Yuan, X. and Dropmann, A. and Maass, T. and Teufel, A. and Marhenke, S. and Gaiser, T. and Rueckert, F. and Kleiter, I. and Kanzler, S. and Ebert, M. P. and Vogel, A. and ten Dijke, P. and Dooley, S. and Meindl-Beinker, N. M. (2017) Hepatocyte-specific Smad7 deletion accelerates DEN-induced HCC via activation of STAT3 signaling in mice. ONCOGENESIS, 6: e294. ISSN 2157-9024,
Full text not available from this repository. (Request a copy)Abstract
TGF-beta signaling in liver cells has variant roles in the dynamics of liver diseases, including hepatocellular carcinoma (HCC). We previously found a correlation of high levels of the important endogenous negative TGF-beta signaling regulator SMAD7 with better clinical outcome in HCC patients. However, the underlying tumor-suppressive molecular mechanisms are still unclear. Here, we show that conditional (TTR-Cre) hepatocyte-specific SMAD7 knockout (KO) mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine (DEN) challenge, verifying SMAD7 as a tumor suppressor in HCC. In line with our findings in patients, Smad7 levels in both tumor tissue as well as surrounding tissue show a significant inverse correlation with tumor numbers. SMAD7 KO mice presented with increased pSMAD2/3 levels and decreased apoptosis in the tumor tissue. Higher tumor incidence was accompanied by reduced P21 and upregulated c-MYC expression in the tumors. Activation of signal transducer and activator of transcription factor 3 signaling was found in Smad7-deficient mouse tumors and in patients with low tumoral SMAD7 expression as compared with surrounding tissue. Together, our results provide new mechanistic insights into the tumor-suppressive functions of SMAD7 in hepatocarcinogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN HEPATOCELLULAR-CARCINOMA; TGF-BETA; OXIDATIVE STRESS; LIVER-CANCER; MOUSE-LIVER; COMPENSATORY PROLIFERATION; IN-VITRO; KAPPA-B; CELLS; HEPATOCARCINOGENESIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:57 |
| Last Modified: | 22 Feb 2019 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/73 |
Actions (login required)
 |
View Item |
