Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks

  • Authors:
    • Alastair G. Lowrie
    • Paul Dickinson
    • Nicholas Wheelhouse
    • Grant D. Stewart
    • Alan J. Ross
    • Thorsten Forster
    • James A. Ross
  • View Affiliations

  • Published online on: June 3, 2011     https://doi.org/10.3892/ijo.2011.1064
  • Pages: 709-718
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Abstract

Dermcidin is a candidate oncogene capable of increasing the number of cultured neuronal, breast cancer and prostate cancer cells and improving the survival of hepatic cells. The dermcidin gene encodes the proteolysis-inducing factor core peptide (PIF-CP) and the skin antimicrobial peptide DCD-1. The peptide responsible for inducing proliferation of cells and the mechanisms involved are unknown. In this study, we confirmed a proliferative effect of dermcidin overexpression of 20% (p<0.02) in the HuH7 human hepatic cell line. Proliferation was abrogated by prevention of PIF-CP translation or inactivation of its calcineurin-like phosphatase domain by site-directed mutagenesis. Prevention of DCD-1 translation had no effect. Treatment of cells with a 30 amino acid synthetic PIF-CP induced an analogous increase in proliferation of 14%. Microarray analysis of PIF-CP-treated cells revealed low but significant changes in 111 potential mediator genes. Pathway analysis revealed several gene networks involved in the cellular response to the peptide, one with VEGFB as a hub and two other networks converging on FOS and MYC. Quantitative PCR confirmed direct upregulation of VEGFB. These data reveal PIF-CP as the key mediator of dermcidin-induced proliferation and demonstrate induction of key oncogenic pathways.

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September 2011
Volume 39 Issue 3

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

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Spandidos Publications style
Lowrie AG, Dickinson P, Wheelhouse N, Stewart GD, Ross AJ, Forster T and Ross JA: Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks. Int J Oncol 39: 709-718, 2011
APA
Lowrie, A.G., Dickinson, P., Wheelhouse, N., Stewart, G.D., Ross, A.J., Forster, T., & Ross, J.A. (2011). Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks. International Journal of Oncology, 39, 709-718. https://doi.org/10.3892/ijo.2011.1064
MLA
Lowrie, A. G., Dickinson, P., Wheelhouse, N., Stewart, G. D., Ross, A. J., Forster, T., Ross, J. A."Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks". International Journal of Oncology 39.3 (2011): 709-718.
Chicago
Lowrie, A. G., Dickinson, P., Wheelhouse, N., Stewart, G. D., Ross, A. J., Forster, T., Ross, J. A."Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks". International Journal of Oncology 39, no. 3 (2011): 709-718. https://doi.org/10.3892/ijo.2011.1064