Information de reference pour ce titreAccession Number: | 00003970-200802000-00025.
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Author: | Hellerbrand, C 1; Amann, T 1,2; Schlegel, J 2; Wild, P 3; Bataille, F 3; Spruss, T 4; Hartmann, A 2; Bosserhoff, A-K 2
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Institution: | (1)Department of Internal Medicine I, University of Regensburg, Germany (2)Institute of Pathology, University of Regensburg, Germany (3)Department of Pathology, University of Zurich, Switzerland (4)Institute of Pharmacy, University of Regensburg, Germany
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Title: | The novel gene MIA2 acts as a tumour suppressor in hepatocellular carcinoma.[Miscellaneous Article]
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Source: | Gut. 57(2):243-251, February 2008.
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Abstract: | Background: Melanoma inhibitory activity 2 (MIA2) is a novel gene of the MIA gene family. The selective expression of MIA2 in hepatocytes is controlled by hepatocyte nuclear factor (HNF) 1 binding sites in the MIA2 promotor. In contrast, in most hepatocellular carcinomas (HCC) MIA2 expression is down-regulated or lost.
Aim: In this study we examined the regulation and functional role of MIA2 in hepatocancerogenesis.
Methods and results: In HCC cell lines and tissues HNF-1 expression was lower than in primary human hepatocytes (PHH) and corresponding non-tumorous tissue, respectively, and correlated significantly with the down-regulation of MIA2 expression. Re-expression of HNF-1 in HCC cells reinduced MIA2 in HCC cells to similar levels as found in PHH. Further, MIA2 was re-expressed in HCC cell lines by stable transfection, and the generated cell clones revealed a strongly reduced invasive potential and proliferation rate in vitro. In line with these findings treatment of HCC cells with recombinant MIA2 inhibited proliferation and invasion. In nude mice MIA2 re-expressing HCC cells grew significantly slower and revealed a less invasive growth pattern. Immunohistochemical analysis of a tissue microarray containing HCC and corresponding non-cancerous liver tissue of 85 patients confirmed reduced MIA2 expression in HCC. Furthermore, MIA2 negative HCC tissue showed a significantly higher Ki67 labelling index and loss of MIA2 expression correlated significantly with more advanced tumour stages.
Conclusion: This study presents MIA2 as an inhibitor of HCC growth and invasion both in vitro and in vivo, and consequently, as a tumour suppressor of HCC. Further, our findings indicate a novel mechanism, how loss of HNF-1 expression in HCC affects tumorigenicity via down-regulation of MIA2.
(C) 2008 BMJ Publishing Group Ltd and the British Society of Gastroenterology
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Language: | English.
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Document Type: | Hepatology.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0017-5749
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NLM Journal Code: | fvt, 2985108r
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DOI Number: | https://dx.doi.org/10.1136/gut.2...- ouverture dans une nouvelle fenêtre
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