Glucocorticoid antagonist RU 486 reverses agonist-induced apoptosis and c-myc repression in human leukemic CEM-C7 cells.
A synthetic glucocorticoid dexamethasone (DEX) inhibits proliferation and induces apoptosis of clone CEM-C7 cells, but not in clone CEM-C1 cells, even though they contain glucocorticoid receptors (GR). We previously showed that suppression of c-myc is a critical step in glucocorticoid-induced cell lysis of C7 cells. It is not reduced in C1 cells. In this study we review the basis for this conclusion and present evidence that the glucocorticoid antagonist RU 486 rescues DEX-treated C7 cells from cell death. An increase in DEX-repressed c-myc mRNA levels precedes the recovery of cell growth. A threshold level of Myc expression appears to be required to maintain growth and viability of C7 cells. Although C1 cells are highly resistant to lysis by glucocorticoids, addition of forskolin, an inducer of protein kinase A, synergizes to evoke complete apoptosis. This synergistic effect is prevented by RU 486, indicating direct involvement of the GR.
Thompson
E B
EB
University of Texas Medical Branch, Department of Human Biological Chemistry and Genetics, Galveston 77550, USA.
Thulasi
R
R
Saeed
M F
MF
Johnson
B H
BH
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D008954:Models, Biological; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D017868:Cyclic AMP-Dependent Protein Kinases