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Cells en route to apoptosis are characterized by the upregulation of c‐fos, c‐myc, c‐jun, cdc2 , and RB phosphorylation, resembling events of early cell‐cycle traverse
Author(s) -
Pandey Siyaram,
Wang Eugenia
Publication year - 1995
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240580203
Subject(s) - cell cycle , cyclin dependent kinase 1 , proliferating cell nuclear antigen , apoptosis , dna fragmentation , c jun , biology , downregulation and upregulation , microbiology and biotechnology , programmed cell death , fragmentation (computing) , cell growth , gene , transcription factor , genetics , ecology
Density‐arrested quiescent murine Balb/c‐3T3 cells are dependent upon growth factors for their survival. Withdrawal of serum from their medium induces rapid cell death, the mechanism of which is not yet fully understood. We have studied the effect of serum deprivation on density‐inhibited quiescent Swiss 3T3 cells and found that they undergo rapid cell death upon total withdrawal of serum. The nature of this cell death is similar to apoptosis, as shown by cellular and nulear morphology and DNA fragmentation into oligonucleosomal fragments. Investigating the regulation of early cell‐cycle genes during this process, we found that c‐myc, c‐jun, c‐fos , and cdc2 , protein presence is induced after serum deprivation, when the phosphorylated form of the RB protein also appears. The upregulation of these genes' protein products is coupled with the appearance of PCNA, a proliferation‐specific nuclear antigen, as well as significant incorporation of BrdU, which may reflect DNA repair activity; in situ analysis shows that BrdU‐positive cells are also positive for DNA fragmentation. These results suggest that en route to apoptosis, cells undergo events typical of early cell‐cycle traverse by expressing early G 1 genes and may even experience the late G 1 /S phase boundary, as shown by the presence of PCNA. However, the demonstrated ability of these cells to traverse the G 1 phase of the cell cycle seems to be an abortive event, since they die shortly afterwards.