کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1929005 1536781 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ETV6–NTRK3 as a therapeutic target of small molecule inhibitor PKC412
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
ETV6–NTRK3 as a therapeutic target of small molecule inhibitor PKC412
چکیده انگلیسی

The ETV6–NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was first identified by cloning of the t(12;15)(p13;q25) translocation in congenital fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia (AML). Using IMS-M2 and M0–91 cell lines harboring the EN fusion gene, and Ba/F3 cells stably transfected with EN, we demonstrated that PKC412, also known as midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412 suppressed the activity of it downstream molecules leading to inhibition of cell proliferation and induction of apoptosis. Our data for the first time suggested that PKC412 could serve as therapeutic drug for treatment of patients with this fusion.


► ETV6–NTRK3 is an oncogene with transformation activity in multiple cell lineages.
► PKC412 could block ETV6–NTRK3 activation.
► Loss of ETV6–NTRK3 phosphorylation leads to inactivation of its downstream signaling pathway.
► Inhibition of ETV6–NTRK3 activation by PKC412 could be a novel strategy for the treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 429, Issues 1–2, 7 December 2012, Pages 87–92
نویسندگان
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