Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells.
- Author:
Kyung Mi KIM
1
;
Kee Hyun LEE
;
Young Sook HONG
;
Hae Young PARK
Author Information
1. Department of Biochemistry and Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
Apoptosis;
Fas;
DcR3;
FAP-1;
Bcl-2;
Bax;
cycloheximide
- MeSH:
Antigens, CD95/*metabolism;
Apoptosis/drug effects/*genetics;
Carrier Proteins/biosynthesis/genetics;
Comparative Study;
Cycloheximide/pharmacology;
Gene Expression Regulation, Neoplastic;
Hematologic Neoplasms/*genetics/metabolism;
Human;
Membrane Glycoproteins/*metabolism;
Protein Synthesis Inhibitors/pharmacology;
Protein-Tyrosine-Phosphatase/biosynthesis/genetics;
Proto-Oncogene Proteins/biosynthesis/genetics;
Proto-Oncogene Proteins c-bcl-2/biosynthesis/genetics;
Receptors, Cell Surface/biosynthesis/genetics;
Signal Transduction;
Support, Non-U.S. Gov't;
Tumor Cells, Cultured
- From:Experimental & Molecular Medicine
2000;32(4):246-254
- CountryRepublic of Korea
- Language:English
-
Abstract:
Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.
