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lüll 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

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Nephropedia PMID record
{{recpmid|pmid=18511292|ti=Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24 |au=Ekmekcioglu S; Mumm JB; Udtha M; Chada S; Grimm EA|so=Cytokine 2008; 43 (1): 34-44|ab=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.}}
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{{BibRecord | Autor = Ekmekcioglu S; Mumm JB; Udtha M; Chada S; Grimm EA | Titel = Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24 | Band = 43 | Nummer = 1 | Jahr = 2008 | Monat = Jul | Sprache = eng | DOI = | Seite = 34-44 | PMID = 18511292 | Typ= {{{Typ|}}} | Kommentar = {{{Kommentar|}}} | format = {{{format|}}} | record = {{{record|}}} }}

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