PMID- 9566690
OWN - NLM
STAT- MEDLINE
DCOM- 19980508
LR  - 20190720
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 125
IP  - 1-2
DP  - 1998 Mar 13
TI  - Increased susceptibility of the c-Myc overexpressing cell line, SNU-16, to 
      TNF-alpha.
PG  - 17-23
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional 
      cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells. 
      However, the molecular mechanisms by which tumor cells become sensitive to the 
      cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that 
      the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor 
      cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high 
      due to gene amplification, showed programmed cell death detected by DNA 
      fragmentation and morphological changes. An antisense c-myc S-oligonucleotide 
      specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided 
      that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western 
      immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha 
      increased the level of these proteins in a time-dependent manner and that this 
      effect lasted for 12 h. Taken together these data indicate that the deregulation 
      of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha. 
      Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased 
      expression of p53 and Bax protein levels following TNF-alpha treatment. 
      Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to 
      tumor cells, is coupled with a p53 and Bax apoptotic pathway.
FAU - Park, I C
AU  - Park IC
AD  - Laboratory of Cell Biology, Korea Cancer Center Hospital, Seoul, South Korea.
FAU - Park, M J
AU  - Park MJ
FAU - Lee, S H
AU  - Lee SH
FAU - Choe, T B
AU  - Choe TB
FAU - Jang, J J
AU  - Jang JJ
FAU - Hong, S I
AU  - Hong SI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (BAX protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - Apoptosis/drug effects
MH  - *Genes, myc
MH  - Humans
MH  - Proto-Oncogene Proteins/analysis/physiology
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - Stomach Neoplasms/*genetics/pathology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Tumor Suppressor Protein p53/analysis/physiology
MH  - bcl-2-Associated X Protein
EDAT- 1998/05/05 00:00
MHDA- 1998/05/05 00:01
CRDT- 1998/05/05 00:00
PHST- 1998/05/05 00:00 [pubmed]
PHST- 1998/05/05 00:01 [medline]
PHST- 1998/05/05 00:00 [entrez]
AID - S0304-3835(97)00450-3 [pii]
AID - 10.1016/s0304-3835(97)00450-3 [doi]
PST - ppublish
SO  - Cancer Lett. 1998 Mar 13;125(1-2):17-23. doi: 10.1016/s0304-3835(97)00450-3.