Silencing of PKCη induces cycle arrest of EBV(+) B lymphoma cells by upregulating expression of p38-MAPK/TAp73/GADD45α and increases susceptibility to chemotherapeutic agents

Ga Bin Park; Yunock Choi; Yeong-Seok Kim; Hyun-Kyung Lee; Daejin Kim; Dae Young Hur

doi:10.1016/j.canlet.2014.04.020

Silencing of PKCη induces cycle arrest of EBV(+) B lymphoma cells by upregulating expression of p38-MAPK/TAp73/GADD45α and increases susceptibility to chemotherapeutic agents

Cancer Lett. 2014 Aug 1;350(1-2):5-14. doi: 10.1016/j.canlet.2014.04.020. Epub 2014 Apr 28.

Authors

Ga Bin Park¹, Yunock Choi¹, Yeong-Seok Kim¹, Hyun-Kyung Lee², Daejin Kim¹, Dae Young Hur³

Affiliations

¹ Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
² Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
³ Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea. Electronic address: dyhur@inje.ac.kr.

PMID: 24784886
DOI: 10.1016/j.canlet.2014.04.020

Abstract

PKCη is involved in proliferation, differentiation, and drug resistance. However, PKCη function in EBV(+) B lymphoma remains poorly understood. Gene silencing of PKCη through siRNA knockdown inhibited cellular proliferation, induced cell cycle arrest in G0/G1 and G2/M phases, and sensitized cells to chemotherapeutic drugs. Upon PKCη knockdown, expression levels of p21, GADD45α, and TAp73 were all increased, whereas expression levels of CDK2, CDK4, CDK6, cyclin E, cyclin B1, and cdc2 were all downregulated. PKCη silencing also activated p38-MAPK, which in turn contributed to the expression of cell cycle arrest-related molecules. These results suggest that siRNA-mediated silencing of PKCη can be a potent tool to complement existing chemotherapy regimens for treating EBV(+) B lymphoma.

Keywords: Cell cycle arrest; EBV(+) lymphoma; GADD45α; PKCη; TAp73; p38-MAPK.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / therapeutic use*
Apoptosis / drug effects
Apoptosis / genetics
Boronic Acids / therapeutic use
Bortezomib
Burkitt Lymphoma / drug therapy*
Burkitt Lymphoma / genetics
Cell Cycle Checkpoints / genetics
Cell Cycle Proteins / biosynthesis
Cell Division / genetics
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p21 / genetics
DNA-Binding Proteins / biosynthesis
Drug Resistance, Neoplasm / genetics*
Herpesvirus 4, Human*
Humans
Membrane Potential, Mitochondrial
NF-kappa B / genetics
Niacinamide / analogs & derivatives
Niacinamide / therapeutic use
Nuclear Proteins / biosynthesis
Phenylurea Compounds / therapeutic use
Phosphatidylinositol 3-Kinases / genetics
Protein Kinase C / genetics*
Protein Kinase C / metabolism
Pyrazines / therapeutic use
RNA Interference
RNA, Small Interfering / genetics
Sorafenib
Tumor Protein p73
Tumor Suppressor Proteins / biosynthesis
Up-Regulation
p38 Mitogen-Activated Protein Kinases / biosynthesis

Substances

Antineoplastic Agents
Boronic Acids
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p21
DNA-Binding Proteins
GADD45A protein, human
NF-kappa B
Nuclear Proteins
Phenylurea Compounds
Pyrazines
RNA, Small Interfering
Tumor Protein p73
Tumor Suppressor Proteins
Niacinamide
Bortezomib
Sorafenib
Phosphatidylinositol 3-Kinases
protein kinase C eta
Protein Kinase C
p38 Mitogen-Activated Protein Kinases