• e2f1-mediated dna damage is implicated in 8-cl-adenosine-induced chromosome missegregation and apoptosis in human lung cancer h1299 cells

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    • تاریخ ارائه: 1392/07/24
    • تاریخ انتشار در تی پی بین: 1392/07/24
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     although e2f1-mediated dna double-stranded breaks (dsbs) and tetraploid have been extensively studied, the role of e2f1 in mitotic catastrophe is still unknown. we have previously shown that 8-chloro-adenosine (8-cl-ado) induces dna dsbs and aberrant mitosis in human lung cancer cells, followed by delayed apoptosis. here, we demonstrate that e2f1-mediated dna damage is implicated in 8-cl-ado-induced chromosome missegregation and apoptosis in lung cancer h1299 cells. we showed that e2f1 was accumulated upon 8-cl-ado-induced dna dsbs. induction of e2f1 by 8-cl-ado caused dna damage in cycling cells including m cells. in contrast, silencing of e2f1 expression decreased 8-cl-ado-induced dna dsbs, particularly eliminated e2f1-mediated mitotic dna damage. over-expression of e2f1 and/or 8-cl-ado exposure resulted in aberrant mitotic spindles and chromosome segregation errors. furthermore, over-expression of e2f1 expression enhanced 8-cl-ado-induced apoptosis. together, our data indicate that e2f1-mediated dna damage, in particular mitotic dna damage, is an important fraction of 8-cl-ado-induced dna damage, which is implicated in 8-cl-ado-induced mitotic catastrophe and delayed apoptosis. induction of e2f1 by 8-cl-ado may contribute at least partly to the drug-inhibited proliferation of cancer cells.

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