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dc.contributor.authorEkmekcioglu, Suhendan
dc.contributor.authorMumm, John B.
dc.contributor.authorUdtha, Malini
dc.contributor.authorChada, Sunil
dc.contributor.authorGrimm, Elizabeth A.
dc.date2022-08-11T08:08:52.000
dc.date.accessioned2022-08-23T16:10:32Z
dc.date.available2022-08-23T16:10:32Z
dc.date.issued2008-05-31
dc.date.submitted2009-02-24
dc.identifier.citationCytokine. 2008 Jul;43(1):34-44. Epub 2008 Jun 3. <a href="http://dx.doi.org/10.1016/j.cyto.2008.04.010">Link to article on publisher's site</a>
dc.identifier.issn1096-0023 (Electronic)
dc.identifier.doi10.1016/j.cyto.2008.04.010
dc.identifier.pmid18511292
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32957
dc.description.abstractRestoration 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18511292&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.cyto.2008.04.010
dc.subjectCell Death; Cell Line; Cell Line, Tumor; Coculture Techniques; Humans; Interferon-alpha; Interferon-beta; Interleukins; Melanoma; Signal Transduction; Up-Regulation
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleKilling of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24
dc.typeJournal Article
dc.source.journaltitleCytokine
dc.source.volume43
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1509
dc.identifier.contextkey738077
html.description.abstract<p>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.</p>
dc.identifier.submissionpathgsbs_sp/1509
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.contributor.departmentDepartment of Experimental Therapeutics
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages34-44


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