کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2037399 1072316 2009 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation
چکیده انگلیسی

SummaryInflammation is linked clinically and epidemiologically to cancer, and NF-κB appears to play a causative role, but the mechanisms are poorly understood. We show that transient activation of Src oncoprotein can mediate an epigenetic switch from immortalized breast cells to a stably transformed line that forms self-renewing mammospheres that contain cancer stem cells. Src activation triggers an inflammatory response mediated by NF-κB that directly activates Lin28 transcription and rapidly reduces let-7 microRNA levels. Let-7 directly inhibits IL6 expression, resulting in higher levels of IL6 than achieved by NF-κB activation. IL6-mediated activation of the STAT3 transcription factor is necessary for transformation, and IL6 activates NF-κB, thereby completing a positive feedback loop. This regulatory circuit operates in other cancer cells lines, and its transcriptional signature is found in human cancer tissues. Thus, inflammation activates a positive feedback loop that maintains the epigenetic transformed state for many generations in the absence of the inducing signal.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 139, Issue 4, 13 November 2009, Pages 693–706
نویسندگان
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