E2F1 enhances 8-chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells
| Autor: | Ji-Xiang Cao, Jun-Juan Qi, Hong-Ying Duan, Shu-Yan Li, Ju-Hua Ni, Wang-Wei Cai, Guo-Shun An, Guo-Sheng Wu, Hong-Ti Jia |
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| Rok vydání: | 2012 |
| Předmět: |
endocrine system
Lung Neoplasms 2-Chloroadenosine DNA damage Adenocarcinoma of Lung Antineoplastic Agents Apoptosis Biology Adenocarcinoma Biochemistry chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor E2F1 Humans Cell Proliferation Cell growth E2F1 Transcription Factor General Medicine Transfection Cell biology G2 Phase Cell Cycle Checkpoints chemistry M Phase Cell Cycle Checkpoints biological phenomena cell phenomena and immunity DNA DNA Damage |
| Zdroj: | Biochemistry. Biokhimiia. 77(3) |
| ISSN: | 1608-3040 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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