Suppression of c-myc and c-myb expression in myeloid cell lines treated with recombinant tumor necrosis factor-alpha.
Proto-oncogenes are thought to be involved in cellular differentiation and proliferation. Tumor necrosis factors (TNFs) are specific cytokines that have cytostatic and cytotoxic effects in vitro against a wide range of human tumor cells. We have previously demonstrated that recombinant TNFs (rTNFs) have an antiproliferative effect on certain human leukemic cell lines (HL-60, KBM3, KBM5) and no effect on others (K562). To study the possible role of the c-myc and c-myb oncogenes in this antiproliferative effect of TNF, we examined their expression in cell lines HL-60, KBM3, KBM5, and K562 before and after incubation with rTNF-alpha. Expression of c-myc and c-myb was elevated in all cell lines prior to incubation with rTNF-alpha. In the sensitive cell lines HL-60, KBM5, and KBM3 expression of c-myc and c-myb decreased rapidly 8-, 16-, and 4-fold, respectively, by 24 hr. K562 cells, insensitive to rTNF-alpha, exhibited no change in c-myc or c-myb expression over 24 hr. These studies demonstrated that down-regulation of c-myc and c-myb expression were associated with antiproliferative effects of rTNF-alpha on these cell lines.
Schachner
J
J
Department of Hematology, M. D. Anderson Hospital and Tumor Institute, Houston, TX 77030.
Blick
M
M
Freireich
E
E
Gutterman
J
J
Beran
M
M
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha