PMID- 12688321
OWN - NLM
STAT- MEDLINE
DCOM- 20030822
LR  - 20190116
IS  - 1042-8194 (Print)
IS  - 1026-8022 (Linking)
VI  - 44
IP  - 3
DP  - 2003 Mar
TI  - Activation of protein kinase C enhances TNF-alpha-induced differentiation by 
      preventing apoptosis via rapid up-regulation of c-Myc protein expression in HL-60 
      cells.
PG  - 497-503
AB  - Tumor necrosis factor-alpha (TNF-alpha) induces both rapid onset of apoptosis and 
      monocytic differentiation in HL-60 human myeloid leukemia cells. In this study, 
      we examined the effect of activation of protein kinase C (PKC) in c-Myc protein 
      expression in association with the induction of apoptosis and differentiation in 
      TNF-alpha-treated HL-60 cells. Pretreatment with phorbol 12-myristate 13-acetate 
      (PMA), an activator of PKC, prevented TNF-alpha-induced rapid onset of apoptosis, 
      which occurs at 3 h culture with TNF-alpha, concomitantly with the up-regulation 
      of c-Myc protein expression. In addition, PMA enhanced TNF-a-induced 
      differentiation at 24h treatment. This was documented by the expression of 
      integrin Mac-1 molecule (CD11b) on the cell surface and the cellular adhesion to 
      the plastic bottom of the flask, indicating the differentiation along with the 
      monocyte/macrophage lineage. These results indicate that activation of PKC not 
      only counteracts apoptosis but also enhances differentiation in TNF-alpha-treated 
      HL-60 cells. Up-regulation of c-Myc protein evoked by pretreatment with PMA for a 
      short time could disturb the signaling pathway of the ceramide and sphingosine, 
      which are known to function as the endogenous modulators mediating the apoptotic 
      signal of TNF-alpha. Our results strongly suggest the role of c-Myc protein as a 
      mediator of cytoprotective effect of PKC pathway, and PKC pathway opposes 
      apoptosis and consequently undergo differentiation via rapid up-regulated c-Myc 
      protein expression during TNF-alpha signaling of HL-60 cells. Our findings 
      provide a new insight for a role of PKC and c-Myc protein with special reference 
      to the regulatory mechanisms in the decision of cellular fate, differentiation or 
      apoptosis.
FAU - Kumakura, Shunichi
AU  - Kumakura S
AD  - Division of Blood Transfusion, Shimane Medical University, Izumo, 693-8501, 
      Japan. kumakura@shimane-med.ac.jp
FAU - Ishikura, Hiroto
AU  - Ishikura H
FAU - Maniwa, Yasuhisa
AU  - Maniwa Y
FAU - Munemasa, Shoso
AU  - Munemasa S
FAU - Tsumura, Hiroto
AU  - Tsumura H
FAU - Masuda, Junichi
AU  - Masuda J
FAU - Kobayashi, Shotai
AU  - Kobayashi S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (CD11b Antigen)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Apoptosis/*drug effects/physiology
MH  - CD11b Antigen/analysis
MH  - Cell Adhesion/drug effects
MH  - Cell Differentiation/drug effects
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - *Genes, myc
MH  - HL-60 Cells/*drug effects/metabolism
MH  - Humans
MH  - Neoplasm Proteins/*physiology
MH  - Protein Kinase C/*physiology
MH  - Proto-Oncogene Proteins c-myc/*biosynthesis
MH  - Recombinant Proteins/pharmacology
MH  - Tetradecanoylphorbol Acetate/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2003/04/12 05:00
MHDA- 2003/08/23 05:00
CRDT- 2003/04/12 05:00
PHST- 2003/04/12 05:00 [pubmed]
PHST- 2003/08/23 05:00 [medline]
PHST- 2003/04/12 05:00 [entrez]
AID - 10.1080/1042819021000047010 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2003 Mar;44(3):497-503. doi: 10.1080/1042819021000047010.