Abstract
Human monocytic leukemia U937 cells readily undergo apoptosis when they are treated with TNF-α, anti-Fas antibody and anticancer drugs such as etoposide and Ara-C. To study the mechanism of apoptosis, we developed a novel apoptosis-resistant variant, UC, from U937 cells. The UC cells showed resistance to apoptosis induced by TNF-α, anti-Fas antibody, etoposide and Ara-C. Somatic cell hybridization between U937 and UC showed that apoptosis-resistance to TNF-α in UC was genetically recessive and resistance to etoposide was dominant, suggesting that UC has at least two different mutations functionally involved in apoptosis. Mechanistic analysis revealed that UC cells expressed reduced amounts of c-Myc. Transfection of the c-myc gene into UC cells restored the sensitivity of the cells to undergo apoptosis induced by TNF-α and anti-Fas, which attributes apoptosis-resistance in this circumstance to the reduced expression of c-Myc. On the other hand, c-myc transfection into UC cells could not restore their sensitivity to etoposide- and Ara-C-induced apoptosis, arguing against the role of c-myc in chemotherapy-induced apoptosis. However, treating the parental U937 cells with antisense oligonucleotides designed to reduce c-Myc expression rendered the cells resistant to etoposide-induced as well as to TNF-α-induced apoptosis. These results indicate that the reduced expression of c-Myc in UC is strongly associated with the resistance to etoposide-induced apoptosis. Our finding that c-myc transfection into UC could not restore the sensitivity to etoposide-induced apoptosis, suggests UC could have a second mutation that confers resistance to etoposide-induced apoptosis in a genetically dominant manner. Taken together, our present results indicate that c-Myc plays a role in cellular susceptibility to death receptor-mediated and chemotherapy-induced apoptosis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dong, J., Naito, M. & Tsuruo, T. c-Myc plays a role in cellular susceptibility to death receptor-mediated and chemotherapy-induced apoptosis in human monocytic leukemia U937 cells. Oncogene 15, 639–647 (1997). https://doi.org/10.1038/sj.onc.1201237
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201237
Keywords
This article is cited by
-
The centella asiatica juice effects on DNA damage, apoptosis and gene expression in hepatocellular carcinoma (HCC)
BMC Complementary and Alternative Medicine (2014)
-
Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention
Leukemia (2003)
-
Regulation of the New Coexpressed CD55 (Decay-Accelerating Factor) Receptor on Stomach Carcinoma Cells Involved in Antibody SC-1–Induced Apoptosis
Laboratory Investigation (2001)
-
Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycERTM mice
Oncogene (2000)
-
c-Myc does not prevent glucocorticoid-induced apoptosis of human leukemic lymphoblasts
Oncogene (1999)