کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2113570 1084478 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade
چکیده انگلیسی

Aberrant activation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss or inactivation of TSC1/TSC2 protein complex, leads to negative feedback inhibition of Akt. The exact mechanisms of this process are still not fully understood. Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. We demonstrate that STAT3 promotes the transcription of PTEN by directly binding on the PTEN promoter. Elevated PTEN then inhibits the proliferation of Tsc1−/− or Tsc2−/− cells through down-regulation of Akt signaling. Activation of PTEN in this pathway may thus serve as a protective mechanism against hyper-activated mTORC1 mediated tumorigenesis and contribute to the benign nature of tumors caused by loss of either TSC1 or TSC2.


► PTEN is significantly up-regulated in Tsc1−/− or Tsc2−/− MEFs.
► Loss of TSC1/TSC2 up-regulates PTEN through activation of mTORC1-STAT3 pathway.
► STAT3 promotes the expression of PTEN at transcriptional level.
► Elevated PTEN suppresses Akt activity and inhibits the proliferation of Tsc1- or Tsc2-null MEFs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 313, Issue 2, 27 December 2011, Pages 211–217
نویسندگان
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