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Qin Chen, Fang-Cheng Hung, Larry Fromm, Paul A. Overbeek; Induction of Cell Cycle Entry and Cell Death in Postmitotic Lens Fiber Cells by Overexpression of E2F1 or E2F2. Invest. Ophthalmol. Vis. Sci. 2000;41(13):4223-4231.
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purpose. Previous studies have shown that inactivation of the retinoblastoma
tumor suppressor protein (pRb) can cause lens fiber cell proliferation
and apoptosis. Because pRb is thought to block cell cycle progression
by inhibition of E2F transcription factors, experiments were
conducted to test whether overexpression of different E2F family
members would be sufficient to induce fiber cell proliferation and
subsequent apoptosis. The in vivo functions of the transcription factor
E2F2 have not previously been analyzed or described in transgenic mice.
methods. Human E2F1 and E2F2 cDNAs were linked to the αA-crystallin promoter.
Transgenic mice were generated by microinjection. Changes in cell cycle
regulation were assayed by immunohistochemistry for
5-bromo-2′-deoxyuridine (BrdU) incorporation and by in situ
hybridization. Cell death was assayed using the TdT-dUTP terminal
nick-end labeling (TUNEL) assay.
results. At embryonic day (E)15.5, strong expression of the E2F1 and E2F2
transgenes was detected in lens fiber cells with little or no
expression in epithelial cells. BrdU incorporation and TUNEL assays
showed that overexpression of either E2F1 or E2F2 in lens fiber cells
was sufficient to cause cell cycle entry and subsequent apoptosis.
Expression of either E2F1 or E2F2 was sufficient to induce the
transcription of cyclins (A2, B1, and E), as well as p53 and Bax in the
conclusions. Expression of either E2F1 or E2F2 can induce postmitotic lens fiber
cells to re-enter the cell cycle. Inappropriate cell cycle entry is
recognized by p53 in each case, and programmed cell death
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