کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3992648 1258822 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ras Pathway Activation in Malignant Mesothelioma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
Ras Pathway Activation in Malignant Mesothelioma
چکیده انگلیسی

IntroductionMutations in Ras family genes are rare in malignant mesothelioma. The role of activation of the Ras signaling pathway in the pathogenesis of mesothelioma is not clear.MethodsWe studied the activation status of the Ras pathway and the status of other Ras-associated kinases in a panel of human mesothelioma cell lines. In addition, we tested the effect of inhibition of several kinase pathways on mesothelioma cell proliferation. The potential role of kinase signaling on the regulation of cap-dependent translation was also studied.ResultsIn general, Ras-guanosine triphosphate (GTP) was higher in mesothelioma cell lines when compared with a nontransformed mesothelial cell line (LP9). Furthermore, known Ras effectors such as extracellular-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase were found to be active in most of the mesothelioma cell lines tested. Exposure to specific inhibitors of extracellular-regulated kinase 1/2 (U0126) and c-Jun N-terminal kinase (SP600125) significantly decreased the proliferation of H2596 and H2373 cells compared with mock-treated cells. SP600125-mediated c-Jun N-terminal kinase inhibition, but not extracellular-regulated kinase 1/2 inhibition, resulted in a decrease in phosphorylation of 4E-BP1, consequently decreasing cap-dependent activation.ConclusionsThese experiments provide a rationale for targeting Ras and associated signaling pathways in mesothelioma and also suggest cap-dependent translation as one mechanism by which Ras induces proliferation in this disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Thoracic Oncology - Volume 2, Issue 9, September 2007, Pages 789–795
نویسندگان
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