Early response to tumor necrosis factor of human promyelocytic leukemia cell lines sensitive and resistant to the factor.
Early cellular events with respect to protein synthesis and the steady-state level of cellular myc (c-myc) mRNA were analyzed in the tumor necrosis factor (TNF)-sensitive human promyelocytic leukemia cell line HL-60 and in its TNF-resistant variant HL-60R after their exposure to TNF. Addition of TNF at 100 units (U)/ml induced de novo synthesis of two proteins with apparent molecular masses of 100 kDa and 40 kDa in HL-60 cells. The induced synthesis of the 100 kDa protein continued for 6 h, while that of the 40 kDa protein was transient. The 100 kDa protein was detectable in HL-60R cells which were maintained in medium containing 1,000 U/ml TNF, whereas the synthesis of the 40 kDa protein could be transiently induced by TNF at 10(5) U/ml. Dot blot hybridization revealed that the steady-state level of c-myc mRNA in HL-60 cells was transiently reduced by TNF at 100 U/ml but remained at a reduced level for 6 h when 10(5) U/ml TNF was present. In HL-60R cells, TNF at 10(5) U/ml could transiently reduce the c-myc mRNA level. These results showed that induction of the synthesis of a 40 kDa protein and a reduction in the steady-state level of c-myc mRNA were concomitant with cellular sensitivity to the cytostatic action of TNF in HL-60 cells.
Takahashi
K
K
Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Yanoma
S
S
Ono
T
T
D004351:Drug Resistance; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006131:Growth Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha