[Inhibition of proto-oncogene c-myc expression with recombinant human tumor necrosis factor-alpha and interferon-gamma in HL-60 cell lines and acute myelocytic leukemic fresh cells].
HL-60 cell lines and AML fresh bone marrow cells were incubated with rhTNF-alpha and rhIFN-gamma in suspension culture system. Then total RNA was prepared for dot blot with 32P nick-translated c-myc DNA probe. The expression changes of c-myc oncogene when the HL-60 cell lines were treated with rhTNF-alpha and IFN-gamma and the AML fresh bone marrow cells treated with rhTNF-alpha alone were observed. The results showed that when the HL-60 cells were treated with 100U/ml or 500U/ml IFN-gamma and 50U/ml rhTNF-alpha for 8 hours, the expression of c-myc oncogene can be inhibited remarkably. The combination of rhIFN-gamma and rhTNF-alpha shows synergistic effect on inhibition of c-myc expression. High expression of c-myc was found in 8 patients with AML; c-myc mRNA level decreased remarkably after treatment of fresh bone marrow cells with 50U/ml rhTNF-alpha for 12 hours in 6 cases, while the remaining 2 cases showed minimal changes. The results demonstrate that rhTNF-alpha have inhibitive effect on c-myc expression in HL-60 cells and AML fresh leukemic cells. It also indicates the possibility of treating AML with low-dose rhTNF-alpha.
Yuan
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YC
Department of Hematology, Xijing Hospital, 4th Military Medical College, Xian.
Shen
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SY
D000293:Adolescent; D000328:Adult; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma