Expression and involvement of c-fos and c-jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines

Cell death induced by growth factor withdrawal is a programed event in which gene transcription and translation are required. Thus, it is likely that genes encoding for transcriptional factors can play an important role in this process. We have tested this hypothesis by analyzing c-fos and c-jun pro...

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Bibliographic Details
Published in:The Journal of biological chemistry 1992-09, Vol.267 (26), p.18278-18283
Main Authors: COLOTTA, F, POLENTARUTTI, N, SIRONI, M, MANTOVANI, A
Format: Article
Language:English
Subjects:
Ageing, cell death
Base Sequence
Biological and medical sciences
Blotting, Northern
Cell Death - genetics
Cell physiology
DNA, Neoplasm - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression
Genes, fos
Genes, jun
Interleukin-2 - metabolism
Interleukin-6 - metabolism
Molecular and cellular biology
Molecular Sequence Data
Multiple Myeloma - metabolism
Oligonucleotides, Antisense
Proto-Oncogenes
RNA, Messenger - metabolism
Transcription, Genetic
Tumor Cells, Cultured
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Summary:Cell death induced by growth factor withdrawal is a programed event in which gene transcription and translation are required. Thus, it is likely that genes encoding for transcriptional factors can play an important role in this process. We have tested this hypothesis by analyzing c-fos and c-jun protooncogene expression and involvement in lymphoid cells deprived of growth factors. Interleukin (IL)-6- and IL-2-dependent mouse cell lines undergo programmed cell death after growth factor deprivation. Northern blot analysis shows that c-fos and c-jun protooncogenes are rapidly induced (within 60 min) after growth factor deprivation in IL-6- and IL-2-dependent mouse cells. Induction is transient, being undetectable at 120 min after deprivation. Induction of these protooncogenes is at the transcriptional level, as demonstrated by actinomycin D and nuclear run-off experiments. Antisense oligonucleotides directed against c-fos and c-jun mRNAs consistently reduced the expression of these genes in treated cells. This reduction was associated with increased survival of growth factor-deprived lymphoid cells, thus suggesting that the expression of c-fos and c-jun protooncogenes may represent an important early event in the activation of the genetic program of cell death.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(19)36956-x