Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bcl-2 inhibits apoptosis from a variety of stimuli, and a Bcl-2-binding protein BAG-1 also functions in protection from apoptosis in concert with Bcl-2. Here, we provide evidence that prolonged cell survival introduced by overexpression of Bcl-2 or BAG-1 proteins strongly promotes experimental pulmonary metastasis of melanoma B16-BL6 cells. In murine melanoma cell line B16-BL6, gene transfer-mediated expression of the Bcl-2 or BAG-1 led to prolonged cell survival against serum-starved apoptosis in vitro. The Bcl-2-expressing B16 cells, B16-Bcl-2 and the BAG-1-expressing B16 cells, B16-BAG-1 strongly enhanced pulmonary metastasis in allogenic BALB/c nude mice and whole lung weights were increased by 2.4-fold and 1.4-fold, respectively, compared with control transfectants, suggesting that Bcl-2 is a stronger positive modulator of metastasis. When the viable B16-Bcl-2 and control transfectants were injected subcutaneously into BALB/c nude mice, the colony numbers of pulmonary metastasis of the B16-Bcl-2 transfectant increased by 5.6-fold compared with the control transfectants. These enhanced metastatic potentials in the B16-Bcl-2 and the B16-BAG-1 transfectants were well correlated with anti-cell death activity against serum-starvation and enhanced cell viability on limiting dilution. Analysis of the transfectants however revealed that their growth rates, invasive ability and cell motility were not significantly altered by overexpression of either Bcl-2 or BAG-1 proteins. Taken together, these studies demonstrate that prolonged cell survival is a crucial factor to promote metastasis of melanoma, thereby contributing to tumor progression.
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PMID:Anti-cell death activity promotes pulmonary metastasis of melanoma cells. 920 4

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.
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PMID:Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells. 963 44