Z Gastroenterol 2006; 44 - A2_16
DOI: 10.1055/s-2006-931683

The novel gene MIA2 promotes progression of hepatocellular carcinoma

C Hellerbrand 1, T Amann 1, J Schlegel 2, T Spruss 3, F Bataille 2, A Hartmann 2, M Mühlbauer 1, J Schölmerich 1, A Bosserhoff 2
  • 1Klinik und Poliklinik für Innere Medizin I der Universität Regensburg, Regensburg
  • 2Institut für Pathologie der Universität Regensburg, Regensburg
  • 3Institut für Pharmakologie der Universität Regensburg, Regensburg

Recently, we characterized the novel, exclusively in hepatocytes expressed human gene MIA2 1 and demonstrated reduced or lost expression, respectively, of MIA2 in hepatocellular carcinoma (HCC) 2. Here, we aimed to analyze the role of MIA2 in HCC development and progression.

Methods: MIA2 expression was re-induced in hepatoma cells by stable transfection with an MIA2 expression construct, and invasion assays were performed in comparison to mock transfected hepatoma cells. Moreover, growth of MIA2 and mock transfected cell clones was compared in vivo after subcutaneous implantation into nude mice. Furthermore, MIA2 protein expression was analyzed by immunohistochemistry using tissue microarray (TAM) analysis containing HCC tissue and surrounding non-cancerous liver tissue of 390 patients.

Results: In accordance to our previous findings, TAM analysis revealed reduced MIA2 expression in comparison to surrounding non-cancerous liver tissue in 66% of cases and lost MIA2 expression in 48% of HCC cases, respectively. Loss of MIA2 expression correlated significantly with the invasiveness of HCCs. In accordance, the invasive potential of MIA2 re-expressing cell clones was strongly reduced compared to mock transfected cells. Moreover, MIA2 re-expressing cell clones showed a reduced proliferation in vitro and tumors of MIA2 re-expressing cell clones grew significantly slower in nude mice compared to tumors from mock transfected cells.

Summary and Conclusion: Loss of MIA2 expression correlates with the growth and the invasiveness of HCC cells in vitro and in vivo. These data indicate, that MIA2 acts as a tumor suppressor and that loss of MIA2 expression plays a critical role in HCC development and progression.

Literatur: 1. Bosserhoff AK, Moser M, Schölmerich J, Buettner R, Hellerbrand C: Specific expression and regulation of the new MIA-related gene MIA2 in hepatocytes J Biol Chem. 2003; 278:15225-15231 2. Hellerbrand C, Bataille F, Schlegel J, Hartmann A, Mühlbauer M, Schölmerich J, Büttner R, Hofstädter F, Bosserhoff AK: In situ expression patterns of melanoma inhibitory activity 2 (MIA2) in healthy and diseased livers Liver International 2005: 25:357–366