کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4134570 1271464 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nuclear factor–κB activation is associated with somatic and germ line RET mutations in medullary thyroid carcinoma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی آسیب‌شناسی و فناوری پزشکی
پیش نمایش صفحه اول مقاله
Nuclear factor–κB activation is associated with somatic and germ line RET mutations in medullary thyroid carcinoma
چکیده انگلیسی

SummaryThe nuclear factor–κB (NF-κB) family of transcription factors regulates a wide variety of cellular processes including cell growth, differentiation, and apoptosis. NF-κB has been shown to be activated through several signaling pathways that involve growth factor receptors. The aim of the study was to assess the immunohistochemical expression of members of the NF-κB family and the putative targets of NF-κB in a series of medullary thyroid carcinomas (MTCs), in correlation with RET mutational status. A tissue microarray was constructed from paraffin-embedded blocks of 48 MTCs (13 familial, 35 sporadic) previously evaluated for germ line and somatic RET mutations. Immunohistochemical evaluation included members of the NF-κB (p50, p65, p52, c-Rel, RelB) family, as well as putative targets of NF-κB such as Flip, Bcl-xL, and cyclin D1. Nuclear immunostaining for members of NF-κB was frequent in MTCs (p50, 19%; p65, 68%; p52, 86.6%; c-Rel, 75%; RelB, 36%). MTCs with germ line or somatic RET mutations (29 cases) showed NF-κB nuclear translocation (particularly of p65, P = .035) more frequently than MTCs without RET mutations (19 cases). Immunostaining for putative targets of NF-κB showed a significant statistical association between p65 and Bcl-xL (P = .024). In addition, Bcl-xL expression was statistically higher in the tumors with exon 16 RET mutation in comparison with those with exon 10 and 11 RET mutations or wild-type RET (P = .002). Moreover, the significance of RETsignaling in NF-κB activation was evaluated in the RET-mutated TT cell line. TT cells were infected with lentiviruses carrying short hairpin RNA to knock down RET expression, and NF-κB activity was assessed by luciferase reporter assays. Silencing of RET in the TT cell line produced a significant decrease in NF-κB activation and reduction in ERK1/2. The results suggest that the NF-κB is frequently activated in MTCs. The results also support the hypothesis that RET activation by somatic or germ line mutations may be responsible for NF-κB activation in MTCs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Pathology - Volume 39, Issue 7, July 2008, Pages 994–1001
نویسندگان
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