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- Title
Interferon-alpha and transforming growth factor-beta co-induce growth inhibition of human tumor cells.
- Authors
Foser, S; Redwanz, I; Ebeling, M; Heizmann, C W; Certa, U
- Abstract
A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-alpha and transforming growth factor beta-1 (TGF-beta) 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-alpha and TGF-beta, 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-beta activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-alpha and TGF-beta signaling and extends the function of IFN signaling to calcium-sensitive processes.
- Publication
Cellular and molecular life sciences : CMLS, 2006, Vol 63, Issue 19-20, p2387
- ISSN
1420-682X
- Publication type
Journal Article
- DOI
10.1007/s00018-006-6256-7