1. Academic Validation
  2. ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412

ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412

  • Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):87-92. doi: 10.1016/j.bbrc.2012.10.087.
Hoang Thanh Chi 1 Bui Thi Kim Ly Yasuhiko Kano Arinobu Tojo Toshiki Watanabe Yuko Sato
Affiliations

Affiliation

  • 1 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan. kk086406@mgs.k.u-tokyo.ac.jp
Abstract

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.

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