کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2137025 1087829 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rad knockdown induces mitochondrial apoptosis in bortezomib resistant leukemia and lymphoma cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Rad knockdown induces mitochondrial apoptosis in bortezomib resistant leukemia and lymphoma cells
چکیده انگلیسی

To understand the molecular mechanism(s) underlying bortezomib resistance, we sought to identify potential target genes that were differentially expressed in bortezomib-resistant leukemia cells versus parental controls. Microarray analysis revealed that the mRNA levels of Rad (Ras associated with diabetes) were higher in the bortezomib-resistant Jurkat (Jurkat-R) cells than in the parental control cells. The importance of Rad for bortezomib resistance was supported by three observations. First, Rad knockdown overcame bortezomib resistance and induced mitochondrial apoptosis via Noxa/Bcl-2 modulation. Second, Rad decreased cell death in response to bortezomib. Third, leukemia and lymphoma cell lines (K-562, Raji, IM-9 and Jurkat-R) with elevated Rad expression levels showed higher degrees of bortezomib resistance versus those (Sup-B15, JVM-2, U266 and Jurkat) with low Rad expression levels (r = 0.48, P = 0.0004). Thus, Rad over expression could be a molecular target to improve bortezomib sensitivity in human leukemia and lymphoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 36, Issue 9, September 2012, Pages 1172–1178
نویسندگان
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