Expression of proto-oncogene c-jun during differentiation of B-chronic lymphocytic leukemia.
We describe in vitro studies undertaken to characterize the expression of the proto-oncogene c-jun during differentiation of B-CLL cells. The phorbol ester TPA and the natural compound Bryostatin 1 (Bryo) were used to directly stimulate protein kinase C (PKC) while the calcium ionophone A23187 was employed to increase intracellular Ca2+. In quiescent cells c-jun mRNA expression was undetectable or at low levels. Upon treatment with TPA or Bryo, the steady-state levels of c-jun mRNA increased rapidly, reached a maximum at 0.5 or 1 hr, and then decreased in the B-CLL cells from all five patients analyzed; this reaction was augmented by the addition of A23187. Induction of c-jun mRNA by direct stimulation of PKC could be blocked by the PKC inhibitor H7. The present observations, along with other results on the induction of long-term phenotypical cellular changes, such as alteration of morphology and other features of differentiation, support the notion that the second messenger (via PKC) and the third messenger (via proto-oncogene products) pathways are intact in B-chronic lymphocytic leukemia cells.
Gignac
S M
SM
Royal Free Hospital School of Medicine, Department of Haematology, London, U.K.
Buschie
M
M
Pettit
G R
GR
Hoffbrand
A V
AV
Drexler
H G
HG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054713:Bryostatins; D000001:Calcimycin / Q000494:pharmacology; D002454:Cell Differentiation; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018942:Macrolides; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D054713:Bryostatins; D007546:Isoquinolines; D007783:Lactones; C000715470:MAS1 protein, human; D018942:Macrolides; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D000001:Calcimycin; C046785:bryostatin 1; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate