Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma

  • Authors:
    • Marion M. Schuierer
    • Frauke Bataille
    • Thomas S. Weiss
    • Claus Hellerbrand
    • Anja K. Bosserhoff
  • View Affiliations

  • Published online on: September 1, 2006     https://doi.org/10.3892/or.16.3.451
  • Pages: 451-456
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Abstract

The Ras/Raf/MEK/ERK signalling cascade is frequently deregulated in tumourigenic diseases and known to be involved in proliferation and transformation of cells. Also in hepatocellular carcinoma (HCC) increased ERK levels are observed and known to correlate with tumour progression, but the underlying molecular mechanism are unknown. We analyzed expression of Raf-1 kinase inhibitory protein (RKIP) in HCC. Expression of RKIP mRNA and protein was downregulated in HCC cell lines and tissue as compared to primary human hepatocytes (PHH) or non-tumorous liver tissue, respectively. Transfection of an HCC cell line with an RKIP expression construct blocked the Raf kinase pathway resulting in decreased activity of ERK1/2 and AP-1. In contrast, downregulation of RKIP by transfection with an antisense RKIP construct led to increased ERK1/2 and AP-1 activity. Since HCC develop in the majority of cases in cirrhotic liver tissue and cirrhosis is the main risk factor for HCC development, we analyzed RKIP expression also in non-cancerous cirrhotic liver tissues by immunohistochemistry. In contrast to normal liver tissue, where the staining was equally distributed within the cytoplasm, hepatocytes in cirrhotic liver revealed an intense RKIP staining of the membrane. It can be speculated that this changed RKIP expression pattern parallels impaired protein function in PHH in cirrhotic livers that may predispose PHH to malignant transformation. In addition, our study demonstrates functional relevance of downregulation of RKIP in HCC that may play an important role in HCC development and progression.

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September 2006
Volume 16 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Schuierer MM, Bataille F, Weiss TS, Hellerbrand C and Bosserhoff AK: Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma. Oncol Rep 16: 451-456, 2006
APA
Schuierer, M.M., Bataille, F., Weiss, T.S., Hellerbrand, C., & Bosserhoff, A.K. (2006). Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma. Oncology Reports, 16, 451-456. https://doi.org/10.3892/or.16.3.451
MLA
Schuierer, M. M., Bataille, F., Weiss, T. S., Hellerbrand, C., Bosserhoff, A. K."Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma". Oncology Reports 16.3 (2006): 451-456.
Chicago
Schuierer, M. M., Bataille, F., Weiss, T. S., Hellerbrand, C., Bosserhoff, A. K."Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma". Oncology Reports 16, no. 3 (2006): 451-456. https://doi.org/10.3892/or.16.3.451