Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways.

  • Authors:
    • R H Wenger
    • H H Marti
    • C Bauer
    • M Gassmann
  • View Affiliations

  • Published online on: September 1, 1998     https://doi.org/10.3892/ijmm.2.3.317
  • Pages: 317-341
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Abstract

Hypoxia is thought to be a common precursor of coronary artery disease and malignant tumors, both diseases representing the leading causes of death in industrial nations. So far, investigations of oxygen-regulated erythropoietin (EPO) gene expression in the human hepatoma cell lines Hep3B and HepG2 allowed many important insights into the mechanisms of oxygen-sensing, signalling and regulation of an increasing number of oxygen-responsive genes. To differentiate the various signalling pathways involved in EPO production by these two cell lines, we examined several factors that positively influenced EPO expression. The results demonstrate a keen differential effect of cell density and oxygen concentration on EPO induction in Hep3B compared to HepG2 cells. Using optimized cell culture conditions, EPO production rates as high as 1 U EPO per 10(6) Hep3B cells in 24 h could be achieved. We also found a moderate but reproducible positive effect of CoCl2 on hypoxia-induced EPO expression in Hep3B but a negative CoCl2 effect on hypoxic induction in HepG2 cells. CoCl2 inhibited cell growth in a concentration-dependent manner. Interleukin-6 was synergistic with hypoxia on EPO induction in Hep3B as well as HepG2 cells, and dexamethasone enhanced this effect in Hep3B but not in HepG2 cells. The moderate CoCl2-dependent increase of EPO production observed in hypoxic Hep3B cells might indicate that CoCl2 and hypoxia do not necessarily act via, identical signalling pathways.

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Sep 1998
Volume 2 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Wenger R, Marti H, Bauer C and Gassmann M: Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways.. Int J Mol Med 2: 317-341, 1998
APA
Wenger, R., Marti, H., Bauer, C., & Gassmann, M. (1998). Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways.. International Journal of Molecular Medicine, 2, 317-341. https://doi.org/10.3892/ijmm.2.3.317
MLA
Wenger, R., Marti, H., Bauer, C., Gassmann, M."Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways.". International Journal of Molecular Medicine 2.3 (1998): 317-341.
Chicago
Wenger, R., Marti, H., Bauer, C., Gassmann, M."Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways.". International Journal of Molecular Medicine 2, no. 3 (1998): 317-341. https://doi.org/10.3892/ijmm.2.3.317