Amann, Thomas and Maegdefrau, Ulrike and Hartmann, Arndt and Agaimy, Abbas and Marienhagen, Joerg and Weiss, Thomas S. and Stoeltzing, Oliver and Warnecke, Christina and Schoelmerich, Juergen and Oefner, Peter J. and Kreutz, Marina and Bosserhoff, Anja K. and Hellerbrand, Claus (2009) GLUT1 Expression Is Increased in Hepatocellular Carcinoma and Promotes Tumorigenesis. AMERICAN JOURNAL OF PATHOLOGY, 174 (4). pp. 1544-1552. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)Abstract
Accelerated glycolysis is one of the biochemical characteristics of cancer cells. The glucose transporter isoform 1 (GLUT1) gene encodes a key rate-limiting factor in glucose transport into cancer cells. However, its expression level and functional significance in hepatocellular cancer (HCC) are still disputed. Therefore, we aimed to analyze the expression and function of the GLUT1 gene in cases of HCC. We found significantly higher GLUT1 mRNA expression levels in HCC tissues and cell lines compared with primary human hepatocytes and matched nontumor tissue. Immunohistochemical analysis of a tissue microarray of 152 HCC cases revealed a significant correlation between Glut1 protein expression levels and a higher Ki-67 labeling index, advanced tumor stages, and poor differentiation. Accordingly, suppression of GLUT1 expression by siRNA significantly impaired both the growth and migratory potential of HCC cells. Furthermore, inhibition of GLUT1 expression reduced both glucose uptake and lactate secretion. Hypoxic conditions further increased GLUT1 expression levels in HCC cells, and this induction was dependent on the activation of the transcription factor hypoxia-inducible factor-1 alpha. In summary, our findings suggest that increased GLUT1 expression levels in HCC cells functionally affect tumorigenicity, and thus, we propose GLUT1 as an innovative therapeutic target for this highly aggressive tumor. (Am J Pathol 2009, 174:1544-1552, DOI: 10.2353/ajpath.2009.080596)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLUCOSE-TRANSPORTER GLUT1; DIAGNOSTIC UTILITY; HEPATOMA-CELLS; MESSENGER-RNA; LIVER-TUMORS; HYPOXIA; HEPATOCYTES; PROTEIN; CANCER; HEPATOCARCINOGENESIS; |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie Medicine > Abteilung für Nuklearmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Sep 2020 08:35 |
| Last Modified: | 18 Sep 2020 08:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29140 |
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