Related Experiment Videos
Suppression of c-myc and c-myb expression in myeloid cell lines treated with recombinant tumor necrosis factor-alpha
J Schachner1, M Blick, E Freireich
1Department of Hematology, M. D. Anderson Hospital and Tumor Institute, Houston, TX 77030.
Abstract:
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.
Insights
Tumor necrosis factors (TNFs) reduce proliferation in some leukemia cells by decreasing expression of the c-myc and c-myb proto-oncogenes. This finding links TNF
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Proto-oncogenes like c-myc and c-myb regulate cell growth.
- Tumor necrosis factors (TNFs) are cytokines with anti-cancer effects.
- Previous studies showed recombinant TNFs (rTNFs) inhibit certain leukemia cell lines.
Purpose of the Study:
- Investigate the role of c-myc and c-myb proto-oncogenes in TNF-induced antiproliferation.
- Examine the expression of c-myc and c-myb in leukemia cells treated with rTNF-alpha.
Main Methods:
- Assessed c-myc and c-myb gene expression in HL-60, KBM3, KBM5, and K562 cell lines.
- Incubated cell lines with rTNF-alpha and measured changes in proto-oncogene expression over 24 hours.
Main Results:
- c-myc and c-myb expression was initially high in all tested cell lines.
- Sensitive cell lines (HL-60, KBM5, KBM3) showed rapid decreases in c-myc and c-myb expression after rTNF-alpha treatment.
- Insensitive K562 cells displayed no significant change in c-myc or c-myb expression.
Conclusions:
- Down-regulation of c-myc and c-myb expression is associated with the antiproliferative effect of rTNF-alpha.
- Proto-oncogene regulation is a key mechanism in TNF-mediated cancer cell growth inhibition.