1. E2F1 enhances 8-Chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells.
- Author
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Duan, Hong-Ying, Cao, Ji-Xiang, Qi, Jun-Juan, Wu, Guo-Sheng, Li, Shu-Yan, An, Guo-Shun, Jia, Hong-Ti, Cai, Wang-Wei, and Ni, Ju-Hua
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LUNG cancer , *CELL cycle regulation , *ADENOSINES , *APOPTOSIS , *TRANSCRIPTION factors , *CELL proliferation , *DNA damage , *CANCER cells - Abstract
The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in response to DNA damage is less clear. 8-Chloro-adenosine (8-Cl-Ado), a nucleoside analog, can inhibit proliferation in a variety of human tumor cells. However, it is still elusive how the agent acts on tumors. Here we show that A549 and H1299 cells formed DNA double-strand breaks after 8-Cl-Ado exposure, accompanied by E2F1 upregulation at protein level. Overexpressed wild-type (E2F1-wt) colocalized with double-strand break marker γ-H2AX and promoted G2/M arrest in 8-Cl-Ado-exposed A549 and H1299, while expressed S31A mutant of E2F1 (E2F1-mu) significantly reduced ability to accumulate at sites of DNA damage and G2/M arrest, suggesting that E2F1 is required for activating G2/M checkpoint pathway upon DNA damage. Transfection of either E2F1-wt or E2F1-mu plasmid promoted apoptosis in 8-Cl-Ado-exposed cells, indicating that 8-Cl-Ado may induce apoptosis in E2F1-dependent and E2F1-independent ways. These findings demonstrate that E2F1 plays a crucial role in 8-Cl-Ado-induced G2/M arrest but is dispensable for 8-Cl-Ado-induced apoptosis. These data also suggest that the mechanism of 8-Cl-Ado action is complicated. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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