RRC ID 42011
著者 Mori E, Thomas M, Motoki K, Nakazawa K, Tahara T, Tomizuka K, Ishida I, Kataoka S.
タイトル Human normal hepatocytes are susceptible to apoptosis signal mediated by both TRAIL-R1 and TRAIL-R2.
ジャーナル 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
巻・号 11(2)
ページ 203-7
公開日 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
引用数 65
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 U251(RCB0461)