Amann, Thomas and Bataille, Frauke and Spruss, Thilo and Dettmer, Katja and Wild, Peter and Liedtke, Christian and Muehlbauer, Marcus and Kiefer, Paul and Oefner, Peter J. and Trautwein, Christian and Bosserhoff, Anja-Katrin and Hellerbrand, Claus (2010) Reduced Expression of Fibroblast Growth Factor Receptor 2IIIb in Hepatocellular Carcinoma Induces a More Aggressive Growth. AMERICAN JOURNAL OF PATHOLOGY, 176 (3). pp. 1433-1442. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)Abstract
Fibroblast growth factor receptor 2 isoform b (FGFR2-IIIb) is highly expressed in hepatocytes and plays an important role in liver homeostasis and regeneration. Here, we analyzed the expression and function of FGFR2-IIIb in hepatocellular carcinoma (HCC). FGFR-2IIIb expression in HCC tissues and cell lines was lower than in primary human hepatocytes; and nontumorous tissue. FGFR2-IIIb-negative HCCs showed a significantly higher Ki-67 labeling index, and loss of FGFR2-IIIb expression correlated significantly with vascular invasion and more advanced tumor stages. A decrease in FGFR-2IIIb, expression in HCC cell fines was not related to promoter hypermethylation. However, PCR analysis indicated that chromosomal deletion at 10q accounted for the loss of FGFR2 expression in a subset of HCC cells. FGFR2-IIIb re-expression in stable transfected HCC cell lines induced a higher basal apoptosis rate and a significantly reduced proliferation and migratory potential in vitro. In nude mice, FGFR2-IIIb re-expressing HCC cells grew significantly slower, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay revealed higher apoptosis rates. The antitumorigenic effects of FGFR2-IIIb expression in HCC cells were not affected by keratinocyte growth factor or an inhibitor of FGFR-phosphorylation, indicating that they are independent of tyrosine kinase activation. in conclusion, our data indicate that FGFR2-IIIb inhibits tumorigenicity of HCC cells. Identification of the molecular mechanisms promoting regeneration in normal tissue while suppressing malignancy may lead to novel therapeutic targets of this highly aggressive tumor. (Am J Pathol 2010, 176:1433-1442; DOI: 10-2353/ajpath.2010.090356)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNOGLOBULIN-LIKE DOMAIN; EPITHELIAL-CELLS; FGFR2 MUTATIONS; DOWN-REGULATION; HUMAN PROSTATE; IN-VIVO; CANCER; GENE; HYPERMETHYLATION; PROLIFERATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Pathologie Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Aug 2020 12:06 |
| Last Modified: | 03 Aug 2020 12:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24993 |
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