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Publication : Caspase-8 deficiency facilitates cellular transformation in vitro.

First Author  Krelin Y Year  2008
Journal  Cell Death Differ Volume  15
Issue  9 Pages  1350-5
PubMed ID  18566604 Mgi Jnum  J:154263
Mgi Id  MGI:4367545 Doi  10.1038/cdd.2008.88
Citation  Krelin Y, et al. (2008) Caspase-8 deficiency facilitates cellular transformation in vitro. Cell Death Differ 15(9):1350-5
abstractText  Caspase-8 is frequently deficient in several kinds of human tumors, suggesting that certain effects of this enzyme restrict tumor development. To examine the nature of the cellular function whose regulation by caspase-8 contributes to its antitumor effect, we assessed the impact of caspase-8 deficiency on cell transformation in vitro. Caspase-8-deficient mouse embryonic fibroblasts immortalized with the SV40 T antigen did not survive when cultured in soft agar, and were nontumorogenic in nude mice. However, the rate of transformation of these cells during their continuous growth in culture, as reflected in the observed emergence of cells that do grow in soft agar and are able to form tumors in nude mice, was far higher than that of cells expressing caspase-8. These findings indicate that caspase-8 deficiency can contribute to cancer development in a way that does not depend on the enzyme's participation in killing of the tumor cells by host immune cytotoxic mechanisms, or on its involvement in the cell-death process triggered upon detachment of the cells from their substrate, but rather concerns cell-autonomous mechanisms that affect the rate of cell transformation.
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