Research Article

Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 19, pp 2387-2396

First online:

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

  • S. FoserAffiliated withRoche Center for Medical Genomics, F. Hoffmann-La Roche AG
  • , I. RedwanzAffiliated withRoche Center for Medical Genomics, F. Hoffmann-La Roche AG
  • , M. EbelingAffiliated withDepartment of Bioinformatics, F. Hoffmann-La Roche AG
  • , C. W. HeizmannAffiliated withDivision of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich
  • , U. CertaAffiliated withRoche Center for Medical Genomics, F. Hoffmann-La Roche AG Email author 

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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.


Calcium signaling cell proliferation interferon-alpha transforming growth factor-beta S100 proteins