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Expression and significance of Pim‐3 kinase in adult T‐cell leukemia
Author(s) -
Ishikawa Chie,
Senba Masachika,
Hashimoto Tadashi,
Imaizumi Atsushi,
Mori Naoki
Publication year - 2017
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12940
Subject(s) - xiap , cell cycle , kinase , propidium iodide , small interfering rna , viability assay , microbiology and biotechnology , gene knockdown , cell growth , jurkat cells , biology , pim1 , electrophoretic mobility shift assay , cancer research , apoptosis , phosphorylation , cell culture , t cell , programmed cell death , transfection , serine , immunology , gene expression , biochemistry , caspase , immune system , genetics , gene
Background Human T‐cell leukemia virus type 1 ( HTLV ‐1) causes adult T‐cell leukemia ( ATL ). Viral Tax protein plays a major role in ATL development. Pim family of serine/threonine kinases is composed of Pim‐1, ‐2, and ‐3. The potential of Pim family as a target in ATL was analyzed. Methods RT ‐ PCR and Western blotting were used to determine the expression of Pim kinases, Tax, and intracellular signal molecules. Knockdown of Pim‐3 and RelA was performed using small interfering RNA . The effects on cell proliferation, viability, cell cycle, and apoptosis were analyzed by WST ‐8, propidium iodide, and APO 2.7 assay. NF ‐κB DNA binding activity was investigated by electrophoretic mobility shift assay. Results Pim‐3 expression was restricted to HTLV ‐1–infected T‐cell lines. Tax induced Pim‐3 expression through NF ‐κB. Knockdown of Pim‐3 showed growth inhibition of HTLV ‐1–infected T cells. NJC 97‐ NH , a novel inhibitor of the Pim‐1/3 kinases, inhibited cell viability. NJC 97‐ NH induced G2/M cell cycle arrest associated with downregulation of cyclin A and cyclin B1 expression, as well as apoptosis accompanied with downregulation of XIAP and Mcl‐1 expression through inhibition of NF ‐κB pathway, mediated through decrease in IκBα and RelA phosphorylation. Conclusion Pim‐3 is a potentially suitable target for the development of novel therapeutic agents against ATL .