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  • Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24
  • Ekmekcioglu S; Mumm JB; Udtha M; Chada S; Grimm EA
  • Cytokine 2008[Jul]; 43 (1): 34-44
  • Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1-regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN-alpha) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN-gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN-beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN-beta induction followed by IRF regulation and TRAIL/FasL system activation.
  • |Cell Death/physiology[MESH]
  • |Cell Line[MESH]
  • |Cell Line, Tumor[MESH]
  • |Coculture Techniques[MESH]
  • |Humans[MESH]
  • |Interferon-alpha/biosynthesis/*physiology[MESH]
  • |Interferon-beta/biosynthesis/*physiology[MESH]
  • |Interleukins/isolation & purification/*metabolism/physiology[MESH]
  • |Melanoma/*metabolism/*pathology[MESH]
  • |Signal Transduction/*physiology[MESH]
  • |Up-Regulation/physiology[MESH]





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    *<b>[http://www.kidney.de/mlpefetch.php?search=18511292 Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24 ]</b> Cytokine 2008; 43(1) ; 34-44 Ekmekcioglu S; Mumm JB; Udtha M; Chada S; Grimm EA

        *18511292*

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    Cytokine

    34 1.43 2008