Involvement of BCL-2 in glucocorticoid-induced apoptosis of human pre-B-leukemias.
To determine the role of BCL-2 in the glucocorticoid-induced apoptosis of lymphocytes, we analyzed the effect of glucocorticoid on two human pre-B-cell lines which express different levels of BCL-2. Glucocorticoid treatment of the 380 cell line which expresses high levels of BCL-2 resulted in inhibition of cellular proliferation without induction of apoptosis. On the other hand, glucocorticoid treatment of the 697 cell line which expresses lower levels of the BCL-2 resulted in both inhibition of cellular proliferation and apoptosis with characteristic internucleosomal DNA cleavage. The glucocorticoid-induced inhibition of cellular proliferation in both cell lines was also associated with repression of the c-myc mRNA expression. Taken together, our data suggest that BCL-2 blocks the glucocorticoid-induced apoptosis of the 380 pre-B-lymphocytes by extending their survival when the level of c-myc expression is repressed. Also by repressing the expression of c-myc, glucocorticoid causes apoptosis of the 697 pre-B-lymphocytes in the absence of high level of BCL-2 expression.
Alnemri
E S
ES
Department of Pharmacology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Fernandes
T F
TF
Haldar
S
S
Croce
C M
CM
Litwack
G
G
D016923:Cell Death; D002455:Cell Division; D015870:Gene Expression; D016259:Genes, myc; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm