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Blood, 1 January 2001, Vol. 97, No. 1, pp. 227-234
IMMUNOBIOLOGY
Overexpression of E2F-1 leads to cytokine-independent
proliferation and survival in the hematopoietic cell line
BaF-B03
Salvador Gala,
Alexandra Marreiros,
Graeme J. Stewart, and
Peter Williamson
From the Department of Immunology, Westmead Hospital
and Department of Medicine, University of Sydney, Sydney, Australia.
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.
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