Overexpression of E2F-1 leads to cytokine-independent proliferation and survival in the hematopoietic cell line BaF-B03.
Cytokine receptors activate signals that regulate the transcription factor E2F-1, which then coordinates the expression of genes essential for DNA synthesis and cell cycle progression. Overexpression of E2F-1 most often induces S-phase entry followed by apoptosis, but in some cell types it leads to continuous proliferation and transformation. Here, it is shown that constitutive expression of E2F-1 promotes cytokine-independent proliferation in the murine pro-B cell line BaF-B03. There was no enhancement of apoptosis following cytokine withdrawal in these cells, despite the presence of intact p53-dependent apoptotic pathways. Notwithstanding the continuous presence of E2F-1, the cell cycle-dependent expression of cyclin A, cyclin B1, cyclin D1, cyclin E, and proliferating-cell nuclear antigen was restored with a pattern equivalent to that associated with cytokine stimulation. These findings provide evidence that, in the absence of cytokine, constitutive expression of E2F-1 can promote cell cycle progression and prevent apoptosis.
Gala
S
S
Department of Immunology, Westmead Hospital, University of Sydney, Sydney, Australia.
Marreiros
A
A
Stewart
G J
GJ
Williamson
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000187:drug effects; D016213:Cyclins / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004249:DNA Damage / Q000528:radiation effects; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D016207:Cytokines; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D007377:Interleukin-3; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine