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Expression and significance of Pim-3 kinase in adult T-cell leukemia.
- Source :
-
European journal of haematology [Eur J Haematol] 2017 Dec; Vol. 99 (6), pp. 495-504. Date of Electronic Publication: 2017 Sep 11. - Publication Year :
- 2017
-
Abstract
- 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.<br />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 APO2.7 assay. NF-κB DNA binding activity was investigated by electrophoretic mobility shift assay.<br />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. NJC97-NH, a novel inhibitor of the Pim-1/3 kinases, inhibited cell viability. NJC97-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.<br />Conclusion: Pim-3 is a potentially suitable target for the development of novel therapeutic agents against ATL.<br /> (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Apoptosis drug effects
Apoptosis genetics
Cell Cycle drug effects
Cell Cycle genetics
Cell Line, Tumor
Cell Proliferation
Cell Survival
Human T-lymphotropic virus 1
Humans
Leukemia-Lymphoma, Adult T-Cell metabolism
NF-kappa B metabolism
Phosphorylation
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
RNA, Small Interfering
Signal Transduction
Gene Expression Regulation, Neoplastic drug effects
Leukemia-Lymphoma, Adult T-Cell genetics
Protein Serine-Threonine Kinases genetics
Proto-Oncogene Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0609
- Volume :
- 99
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- European journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 28833639
- Full Text :
- https://doi.org/10.1111/ejh.12940