Molecular Endocrinology, Vol 10, 306-316, Copyright © 1996 by Endocrine Society

ARTICLES

Role of c-jun induction in the glucocorticoid-evoked apoptotic pathway in human leukemic lymphoblasts

F Zhou and EB Thompson
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, USA.

Accumulated evidence suggests tI AP-1 family in CEM cell clones exposed to the glucocorticoid dexamethasone (Dex) has been investigated. Dex is known to cause apoptosis of lymphoid cells in general and of sensitive human lymphoid CEM cell clones in particular. This study finds that Dex induces c-jun mRNA and cJun protein in cells of the sensitive clone CEM- C7 and of the lysis-sensitive OEM hybrid clone H10. CEM-O7 cells were screened for several other Jun/Fos family proteins. Both cFos and JunD were expressed but were unaffected by the steroid, and JunB was not detected. In the continual presence of Dex the induction of cJun began about 6 h after addition of Dex, reached a maximum by 24 h, and plateaued for 72 h, while cell death did not begin until 24-48 h. In clone OEM-Cl cells, which contain glucocorticoid receptor (GR) but are resistant to lysis by Dex, the basal, and even the fully induced, cJun levels are below the basal levels in OEM-07 and H10 cells. To test the hypothesis that cJun plays an important role in steroid-evoked apoptosis, stable transfectants expressing Dex-regulable antisense c- jun RNA were established. Mass cultures of these cells showed reduced sensitivity to Dex, and in three of three clones tested, complete resistance to Dex was obtained. This occurred even though endogenous genes (GR, c-jun) normally responsive to Dex were still inducible, indicating that the GR and basic glucocorticoid response apparatus were intact. It is concluded that Dex induces cJun levels in sensitive OEM cells before cell death and that this induction plays a role in the apoptotic process.

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