Protein phosphatase inhibitor-1 mRNA expression correlates with neoplastic transformation of epithelial liver cells and progression of hepatocellular carcinomas

  • Authors:
    • Eiman Aleem
    • Thomas Flohr
    • Heinz Walter Thielmann
    • Peter Bannasch
    • Doris Mayer
  • View Affiliations

  • Published online on: April 1, 2004     https://doi.org/10.3892/ijo.24.4.869
  • Pages: 869-877
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Abstract

Protein phosphatase inhibitor-1 plays an important role in the regulation of glycogen metabolism through inhibition of protein phosphatase-1 activity, and it has been implicated in the regulation of cell growth. Using real-time quantitative RT-PCR, we studied the mRNA expression of inhibitor-1 in hepatocellular carcinomas induced in rats by oral administration of N-nitrosomorpholine, and in a non-tumorigenic liver cell line (C1I), that stores glycogen in excess during early passages. In late passages, glycogen is gradually lost concomitant with cell transformation. Our in vitro model included a tumorigenic subline of C1I cells that was obtained by chemically-induced neoplastic transformation using N-methyl-N'-nitro-N-nitrosoguanidine (C1Ict), and does not store glycogen, as well as Morris hepatoma 3924A (MH3924A) cells. We found that in hepatocellular carcinomas, in the late glycogen-poor passages (C1Ilate), and in the tumorigenic subline (C1Ict) of C1I cells, and in MH3924A cells the mRNA expression of inhibitor-1 is significantly increased. This increase in expression varied from 15 to 290-fold of that observed in normal liver. In contrast, in the early glycogen-storing passage of C1I cells (C1Iearly) the level of inhibitor-1 mRNA was found to be slightly less than that of normal liver. Inhibitor-1 mRNA levels correlated with the degree of differentiation of HCCs. These results indicate that the expression of inhibitor-1 mRNA is tightly linked to tumor progression and to the process of liver cell transformation in vitro and is inversely correlated with the glycogen content of the cell.

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April 2004
Volume 24 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Aleem, E., Flohr, T., Thielmann, H.W., Bannasch, P., & Mayer, D. (2004). Protein phosphatase inhibitor-1 mRNA expression correlates with neoplastic transformation of epithelial liver cells and progression of hepatocellular carcinomas. International Journal of Oncology, 24, 869-877. https://doi.org/10.3892/ijo.24.4.869
MLA
Aleem, E., Flohr, T., Thielmann, H. W., Bannasch, P., Mayer, D."Protein phosphatase inhibitor-1 mRNA expression correlates with neoplastic transformation of epithelial liver cells and progression of hepatocellular carcinomas". International Journal of Oncology 24.4 (2004): 869-877.
Chicago
Aleem, E., Flohr, T., Thielmann, H. W., Bannasch, P., Mayer, D."Protein phosphatase inhibitor-1 mRNA expression correlates with neoplastic transformation of epithelial liver cells and progression of hepatocellular carcinomas". International Journal of Oncology 24, no. 4 (2004): 869-877. https://doi.org/10.3892/ijo.24.4.869