| RRC ID |
42011
|
| Author |
Mori E, Thomas M, Motoki K, Nakazawa K, Tahara T, Tomizuka K, Ishida I, Kataoka S.
|
| Title |
Human normal hepatocytes are susceptible to apoptosis signal mediated by both TRAIL-R1 and TRAIL-R2.
|
| Journal |
Cell Death Differ
|
| Abstract |
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in tumor cells without toxicity to normal cells, but some recombinant versions of TRAIL caused hepatocyte death. We generated fully human monoclonal antibodies (mAbs) that bind specifically to TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), which mediate apoptosis signal when they ligate with TRAIL, to investigate the contribution of each receptor to induce tumor cell apoptosis and hepatocyte toxicity. All of mAbs to TRAIL-R1 and TRAIL-R2 induced cell death in several cancer cell lines susceptible to TRAIL but not in human umbilical vein endothelial cells in vitro. Both anti-TRAIL-R1 mAbs and anti-TRAIL-R2mAbs also caused cell death in hepatocytes. However, a subset of mAbs to TRAIL-R2, which was characterized by the TRAIL blocking activity, did not show strong hepatocyte toxicity. These results indicate that human normal hepatocytes are susceptible to both TRAIL-R1- and TRAIL-R2-mediated apoptosis signal. Cell Death and Differentiation (2004) 11, 203-207. doi:10.1038/sj.cdd.4401331 Published online 24 October 2003
|
| Volume |
11(2)
|
| Pages |
203-7
|
| Published |
2004-2-1
|
| DOI |
10.1038/sj.cdd.4401331
|
| PII |
4401331
|
| PMID |
14576771
|
| MeSH |
Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / toxicity
Apoptosis*
Caspases / metabolism
Cell Line, Tumor
Flow Cytometry
Hepatocytes / cytology*
Hepatocytes / metabolism*
Humans
Mice
Mice, Transgenic
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor / antagonists & inhibitors
Receptors, Tumor Necrosis Factor / immunology
Receptors, Tumor Necrosis Factor / metabolism*
Signal Transduction*
|
| IF |
10.717
|
| Times Cited |
65
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
U251(RCB0461) |
