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| Content Provider | Springer Nature Link |
|---|---|
| Author | Feng, Luo Barnhart, Jerry R. Seeger, Robert C. Wu, Lingtao Keshelava, Ni Huang, Sheng He Jong, Ambrose |
| Copyright Year | 2008 |
| Abstract | The cell division controller Cdc6 plays a central role in the initiation of DNA replication. It was found that elevated levels of Cdc6 were present in many of human cancer cells, and the accumulation of Cdc6 is required for cell proliferation. In this study, we have investigated the control of Cdc6 expression and its effect on cell proliferation and death in human neuroblastoma cells. Elevated levels of Cdc6 are found in the LA-N-2, CHLA255, and other cell lines that grow fast. Cdc6 knockdown via a Cdc6 short hairpin RNA lentivirus causes the accumulation of sub-G1 populations with the decrease of S contents in the LA-N-2 and CHLA255 cells. Expression profile from the selected genes shows the reduction of cyclin E, cyclin A, and Cdc25C, with a boosted increase of the CDK inhibitor p27$^{Kip1}$, indicating the suppression of tumor cell proliferation. Further, Cdc6 knockdown causes the increase of pro-apoptotic Bax accompanied with the decrease of anti-apoptotic Bcl-2, resulting in the increased cell death. Furthermore, Cdc6 knockdown causes a sharp reduction of tumor suppressor protein p53, and Cdc6 overexpression renders a boosted p53 expression; and this regulation is at p53 posttranscriptional level. Our study indicates that human Cdc6 functions in several pathways to control the cell proliferation and the cell death. |
| Starting Page | 189 |
| Ending Page | 197 |
| Page Count | 9 |
| File Format | |
| ISSN | 03008177 |
| Journal | Molecular and Cellular Biochemistry |
| Volume Number | 311 |
| Issue Number | 1-2 |
| e-ISSN | 15734919 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2008-02-08 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Cdc6 shRNA Neuroblastoma Cardiology Oncology Medical Biochemistry Biochemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Clinical Biochemistry Molecular Biology |
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