Dokumentenart: | Artikel | ||||||||||||||||||||||||||||||||||||||||
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Titel eines Journals oder einer Zeitschrift: | The American journal of pathology | ||||||||||||||||||||||||||||||||||||||||
Verlag: | Elsevier | ||||||||||||||||||||||||||||||||||||||||
Band: | 176 | ||||||||||||||||||||||||||||||||||||||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 3 | ||||||||||||||||||||||||||||||||||||||||
Seitenbereich: | S. 1433-42 | ||||||||||||||||||||||||||||||||||||||||
Datum: | März 2010 | ||||||||||||||||||||||||||||||||||||||||
Institutionen: | Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medizin > Lehrstuhl für Innere Medizin I Medizin > Lehrstuhl für Pathologie | ||||||||||||||||||||||||||||||||||||||||
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Klassifikation: |
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Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||||||||||||||||||||||||||||||||||||||
Status: | Veröffentlicht | ||||||||||||||||||||||||||||||||||||||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||||||||||||||||||||||||||||||||||||||
An der Universität Regensburg entstanden: | Zum Teil | ||||||||||||||||||||||||||||||||||||||||
Dokumenten-ID: | 30644 |
Zusammenfassung
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). FGFR2-IIIb expression in HCC tissues and cell lines was lower than in primary human hepatocytes and nontumorous tissue. FGFR2-IIIb-negative ...
Zusammenfassung
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). FGFR2-IIIb 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 lines 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.
Metadaten zuletzt geändert: 29 Sep 2021 07:40