PMID- 9428804 OWN - NLM STAT- MEDLINE DCOM- 19980130 LR - 20071115 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 174 IP - 2 DP - 1998 Feb TI - Genetically recessive mutant of human monocytic leukemia U937 resistant to tumor necrosis factor-alpha-induced apoptosis. PG - 179-85 AB - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces apoptosis in various cell systems by binding to the TNF receptor (TNFR). To study TNF-alpha-induced apoptosis, we isolated and characterized a novel TNF-alpha-resistant variant, U937/TNF clone UA, from human monocytic leukemia U937 cells. The UA cells resist apoptosis induced by TNF-alpha and anti-Fas antibody but not by anticancer drugs, such as VP-16 and Ara-C. Somatic cell hybridization between U937 and UA showed that apoptosis resistance to TNF-alpha in UA was genetically recessive. The hybridization analysis also showed that UA and another recessive mutant clone, UC, belong to different complementation groups in TNF-alpha-induced apoptosis signaling. In UA cells, TNF-alpha-induced disruption of mitochondrial membrane potential and CPP32 activation were abrogated. Expression of TNFR, Fas, and Bcl-2 family proteins was not changed in UA cells. These results suggest that the apoptosis resistant UA cells could have a functional defect in apoptosis signaling from the TNFR to mitochondria and interleukin-1beta converting enzyme (ICE) family protease activation. UA cells could be used to study signaling linkage between cell death-inducing receptor and mitochondria. FAU - Dong, J AU - Dong J AD - Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan. FAU - Naito, M AU - Naito M FAU - Mashima, T AU - Mashima T FAU - Jang, W H AU - Jang WH FAU - Tsuruo, T AU - Tsuruo T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Apoptosis/drug effects/*genetics MH - Genes, Recessive MH - Humans MH - Leukemia, Myeloid/*genetics/pathology MH - *Mutation MH - Signal Transduction/drug effects MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1998/01/15 04:20 MHDA- 2000/06/20 09:00 CRDT- 1998/01/15 04:20 PHST- 1998/01/15 04:20 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1998/01/15 04:20 [entrez] AID - 10.1002/(SICI)1097-4652(199802)174:2<179::AID-JCP5>3.0.CO;2-L [pii] AID - 10.1002/(SICI)1097-4652(199802)174:2<179::AID-JCP5>3.0.CO;2-L [doi] PST - ppublish SO - J Cell Physiol. 1998 Feb;174(2):179-85. doi: 10.1002/(SICI)1097-4652(199802)174:2<179::AID-JCP5>3.0.CO;2-L.