Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 19, pp 2387–2396

Interferon-alpha and transforming growth factor-β co-induce growth inhibition of human tumor cells

  • S. Foser
  • I. Redwanz
  • M. Ebeling
  • C. W. Heizmann
  • U. Certa
Research Article

DOI: 10.1007/s00018-006-6256-7

Cite this article as:
Foser, S., Redwanz, I., Ebeling, M. et al. Cell. Mol. Life Sci. (2006) 63: 2387. doi:10.1007/s00018-006-6256-7

Abstract.

A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-α and transforming growth factor beta-1 (TGF-β) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A DNA microarray-based search for proliferation control genes involved that are cooperatively activated by IFN-α and TGF-β, yielded 28 genes. Among these are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium-binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a potent growth inhibitor requiring TGF-β activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-α in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-α is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-α and TGF-β signaling and extends the function of IFN signaling to calcium-sensitive processes.

Keywords.

Calcium signalingcell proliferationinterferon-alphatransforming growth factor-betaS100 proteins

Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  • S. Foser
    • 1
  • I. Redwanz
    • 1
  • M. Ebeling
    • 2
  • C. W. Heizmann
    • 3
  • U. Certa
    • 1
  1. 1.Roche Center for Medical GenomicsF. Hoffmann-La Roche AGBaselSwitzerland
  2. 2.Department of BioinformaticsF. Hoffmann-La Roche AGBaselSwitzerland
  3. 3.Division of Clinical Chemistry and Biochemistry, Department of PediatricsUniversity of ZurichZürichSwitzerland