کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2795466 1155327 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Killing of human melanoma cells induced by activation of class I interferon-regulated signaling pathways via MDA-7/IL-24
چکیده انگلیسی

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-α) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN-γ), 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-β, 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-β induction followed by IRF regulation and TRAIL/FasL system activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cytokine - Volume 43, Issue 1, July 2008, Pages 34–44
نویسندگان
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