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| Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: Increased binding of cyclin A negatively regulates E2F transactivation activity |
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| Author(s): Turley JM, Ruscetti FW, Kim SJ, Fu T, Gou FV, BirchenallRoberts MC |
| Source: CANCER RESEARCH Volume: 57 Issue: 13 Pages: 2668-2675 Published: JUL 1 1997 |
| Times Cited: 63 References: 73 |
| Abstract: Vitamin E succinate (VES) inhibited the proliferation of the estrogen receptor-negative human breast cancer cell line, BT-20, in the G(1) phase of the cell cycle. The E2F proteins are integral transcriptional components in the regulation of cell growth. Overexpression of E2F-1 blocked the ability of VES to inhibit BT-20 cell growth, suggesting that VES regulation of E2F-1 activity leads to growth arrest of BT-20 cells. VES, although having little effect on E2F-1 steady-state protein levels, decreased E2F-1 phosphorylation and transactivation activity and increased cyclin A binding to E2F-1. GAL4-E2F-1 deletion mutant studies indicated that cyclin A negatively regulates E2F function. In VES-treated BT-20 cells, the cyclin A protein exhibited reduced kinase activity, which correlated with decreased steady-state levels and binding of cyclin-dependent kinase-2 to cyclin A and increased steady-state levels and binding of p21(cip1) to cyclin A and cyclin-dependent kinase-2. The functional consequence of the negative regulatory effect of VES on E2F-1 function was shown by the ability of VES to inhibit the transcriptional activation of an E2F-1 responsive gene, c-myc. These studies show that VES induces growth inhibition of BT-20 cells through a mechanism that involves cyclin A-negative regulation of E2F-mediated transcription. |
| Document Type: Article |
| Language: English |
Addresses:
1. NCI, FREDERICK CANC RES & DEV CTR, INTRAMURAL RES & SUPPORT PROGRAM, SCI APPLICAT INT CORP, FREDERICK, MD 21702 USA
2. NCI, FREDERICK CANC RES & DEV CTR, LAB LEUKOCYTE BIOL, DIV BASIC SCI, FREDERICK, MD 21702 USA
3. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: XG575 |
| ISSN: 0008-5472 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |