Study on the growth inhibition of human multiple myeloma cells by an IL-6Ralpha mutant.
DM650, a soluble human IL-6Ralpha mutant with mutation of C277D/H280I, was previously shown to exhibit an antagonism to IL-6, which resulted in growth-inhibition of human multiple myeloma cell line AF-10 autocrining as the growth-stimulating factor. We investigated here the nature of the growth inhibition by examining cell apoptosis. Flow-cytometric analysis of the DNA fragmentation demonstrated that 7.2% of the AF-10 cells were apoptotic after 24 h of treatment with DM650. The constitutive gene expression of bcl-2 in AF-10 cells indicated that apoptosis suppressed by IL-6 was independent of bcl-2 regulation. The altered gene expression of c-myc and p53 suggested that a novel apoptosis pathway, other than that suppressed by IL-6, might be triggered by a complex of DM650 and IL-6.
Duan
J
J
Institute of Basic Medical Sciences, Beijing, PR China. jbduan@excite.com
Cai
X
X
Wang
L
L
Zhang
S
S
Wang
J
J
D017209:Apoptosis; D002455:Cell Division / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D008954:Models, Biological; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009693:Nucleic Acid Hybridization; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D019947:Receptors, Interleukin-6; D016159:Tumor Suppressor Protein p53; D012313:RNA