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.
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.
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Ga Bin
GB
Park
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Yunock
Y
Choi
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Yeong-Seok
YS
Kim
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Hyun-Kyung
HK
Lee
Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Daejin
D
Kim
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.
Dae Young
DY
Hur
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004854:Herpesvirus 4, Human; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D016328:NF-kappa B / Q000235:genetics; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009687:Nuclear Proteins / Q000096:biosynthesis; D010671:Phenylurea Compounds / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000077157:Sorafenib; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D000097642:GADD45 Proteins
D000970:Antineoplastic Agents; D001897:Boronic Acids; D000069286:Bortezomib; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009536:Niacinamide; D009687:Nuclear Proteins; D010671:Phenylurea Compounds; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D011719:Pyrazines; D034741:RNA, Small Interfering; D000077157:Sorafenib; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C081975:protein kinase C eta
Cell cycle arrest; EBV(+) lymphoma; GADD45α; PKCη; TAp73; p38-MAPK