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  • Original Paper
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Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells

Oncogene volume 20, pages 4629–4639 (2001)Cite this article

Abstract

Sensitivity to glucocorticoid (GC)-evoked apoptosis in lymphoid cell lines correlates closely with GC-mediated suppression of c-Myc expression. To establish a functional role for c-Myc in GC-mediated apoptosis, we have stably expressed MycERTM, the human c-Myc protein fused to the modified ligand-binding domain of the murine estrogen receptor α, in GC-sensitive CEM-C7-14 cells. In CEM-C7-14 cells, MycERTM constitutively imparts c-Myc functions. Cells expressing MycERTM (C7-MycERTM) exhibited a marked reduction in cell death after 72 h in 100 nM dexamethasone (Dex), with 10–20-fold more viable cells when compared to the parental CEM-C7-14 clone. General GC responsiveness was not compromised, as evidenced by Dex-mediated suppression of endogenous c-Myc and cyclin D3, and induction of c-Jun and the glucocorticoid receptor. MycERTM also blunted Dex-mediated upregulation of p27kipI and suppression of the Myc target p53. In comparison to parental CEM-C7-14 cells, Dex-evoked DNA strand breaks were negligible and caspase activation was delayed, but the extent of G1 cell cycle arrest was similar in C7-MycERTM cells. Myc-ERTM did not result in permanent, complete resistance to GC however, and the GC-treated cells eventually died, indicative of redundant or interactive mechanisms in the GC-evoked lytic response of lymphoid cells. Our results emphasize the importance of c-Myc suppression in GC-evoked apoptosis of CEM-C7-14 cells.

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Abbreviations

GCs:

glucocorticoids

GR:

GC receptor

cdks:

cyclin dependent kinases

Dex:

dexamethasone

ER:

estrogen receptor

ERTM:

G525R mutant of ER α

LBD:

ligand binding domain

4HT:

4 hydroxy tamoxifen

TUNEL:

terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-X-nick end labeling

PARP:

poly ADP ribose polymerase

FBS:

fetal bovine serum

PBS:

phosphate buffered saline

AEBSF:

4-[2-aminoethyl]benzensulfonyl fluoride

ECL:

enhanced chemiluminescence

AFC:

7-amido-4-trifluoromethylcoumarin

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Acknowledgements

We thank Dr T Littlewood for providing us with the construct pBpuroMycERTM, Dr Thomas Wood and the staff of the Recombinant DNA Laboratory of the Sealy Center for Molecular Sciences for help with sequence analysis of MycER cDNA isolated from C7-MycERTM#22 cells, and Mr Mark Griffin for assistance with Flow Cytometric analyses. We also thank Ms Betty Johnson for cloning CEM-C7-14 cells and for her laboratory managerial skills. This work was supported by grants from the John Sealy Endowment Fund for Biomedical Research (to RD Medh), the Elsa U. Pardee Foundation (to RD Medh), and the National Cancer Institute (to EB Thompson, 2RO1 CA41047). This work was done in conjunction with the Walls Medical Research Foundation.

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  1. Feng Zhou

    Present address: Life Science Division, National Flow Cytometry Resource, Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, USA

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  1. Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, TX-77555-0645, Texas, USA

    Rheem D Medh, Aixia Wang & E Brad Thompson

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Correspondence to Rheem D Medh or E Brad Thompson.

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Medh, R., Wang, A., Zhou, F. et al. Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells. Oncogene 20, 4629–4639 (2001). https://doi.org/10.1038/sj.onc.1204680

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