Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells.
Bcl-2 and a Bcl-2-binding protein BAG-1 function in protection from apoptosis induced by a variety of stimuli. Deregulated expression of Bcl-2 leads to inhibition of apoptosis and is correlated with development of various cancers. Here, we provide evidence that prolonged cell survival introduced by overproduction of Bcl-2 or BAG-1 strongly enhances peritoneal dissemination of human gastric cancer MKN74 cells. Gene transfer-mediated overexpression of Bcl-2 or BAG-1 led to prolonged cell survival of MKN74 cells against serum-starved apoptosis and anoikis. When the viable transfectants were inoculated into the intraperitoneal cavity of BALB/c nude mice, the Bcl-2-expressing MKN74 cells and the BAG-1-expressing MKN74 cells exhibited strongly enhanced peritoneal dissemination in BALB/c nude mice and whole disseminated tumor weights were increased by 4-fold and 3.3-fold, respectively, compared with the control transfectants. The enhanced peritoneal dissemination of MKN74-Bcl-2 and MKN74-BAG-1 transfectants correlated well with resistance to cell death induced by serum-starvation and anoikis. However, the overexpression of Bcl-2 or BAG-1 caused no significant difference among the transfectants in cell growth rates, either in vitro or in vivo. Taken together, these studies demonstrate that resistance to apoptosis is a crucial factor for development of peritoneal dissemination of human gastric cancer cells.
Yawata
A
A
The First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Adachi
M
M
Okuda
H
H
Naishiro
Y
Y
Takamura
T
T
Hareyama
M
M
Takayama
S
S
Reed
J C
JC
Imai
K
K
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002470:Cell Survival; D004268:DNA-Binding Proteins; D006801:Humans; D009362:Neoplasm Metastasis; D010534:Peritoneal Neoplasms / Q000556:secondary*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors