Hellerbrand, Claus and Muehlbauer, Marcus and Wallner, Susanne and Schuierer, Marion and Behrmann, Iris and Bataille, Frauke and Weiss, Thomas and Schoelmerich, Juergen and Bosserhoff, Anja-Katrin (2006) Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma. CARCINOGENESIS, 27 (1). pp. 64-72. ISSN 0143-3334,
Full text not available from this repository. (Request a copy)Abstract
The methylthioadenosine phosphorylase (MTAP) gene is localized in the chromosomal region 9p21. Here, frequently homozygous deletions occur in several kinds of cancer associated with the loss of tumour suppressor genes as p16 and p15. The aim of this study was to analyse MTAP expression in hepatocellular carcinoma (HCC) and to get an insight into the regulation and functional role of MTAP in hepatocancerogenesis. Compared with primary human hepatocytes MTAP expression was markedly downregulated in three different HCC cell lines as determined by real-time PCR and western blotting. This was not due to genomic losses or mutations but to promoter-hypermethylation. Reduced MTAP-expression was confirmed in vivo in HCC compared with non-cancerous liver tissue on both mRNA and protein levels. To study the functional relevance of the downregulated MTAP expression in HCC, MTAP expression was re-induced in HCC cell lines by stable transfection. In these MTAP re-expressing cell clones the invasive potential was strongly reduced, whereas no effects on cell proliferation were observed in comparison with mock transfected cell clones. Furthermore, in MTAP re-expressing cells interferon (IFN)-alpha and IFN-gamma induced a significantly stronger inhibition of cell proliferation than in mock transfected cells. In conclusion, our results suggest a functional role of MTAP inactivation in HCC development and invasiveness. Furthermore, in the light of a recent report revealing an association between MTAP activity and IFN sensitivity, our findings may have clinical significance for therapeutic strategies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ORNITHINE DECARBOXYLASE ACTIVITY; TUMOR-SUPPRESSOR; POLYAMINE METABOLISM; RECOMBINANT INTERFERON-ALPHA-2B; DOSE INTERFERON-ALPHA-2B; MALIGNANT-MELANOMA; GENE-EXPRESSION; METHYLATION; DELETION; FREQUENCY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Mar 2021 09:41 |
| Last Modified: | 01 Mar 2021 09:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35091 |
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