| Autor: |
Dong, Yan Bin, Yang, Hai Liang, Elliott, Mary Jane, McMasters, Kelly M. |
| Zdroj: |
Tumor Biology (Springer Science & Business Media B.V.); 2003, Vol. 24 Issue 3, p130-139, 10p |
| Abstrakt: |
DNA damage results in an increase in p53 levels, which is required to initiate a p53-mediated cell cycle arrest and/or apoptosis. P53 and MDM-2 form a feedback control loop: while p53 can transactivate the mdm-2 gene, high levels of MDM-2 inhibit p53 transactivation as well as promote rapid degradation of P53. In the present study, we investigated the interaction between endogenous MDM-2 and p53 following UV-induced DNA damage in an MDM-2 overexpression cell line. A human osteosarcoma cell line (OsACL, which contains wild-type p53 and overexpresses MDM-2 protein) was used in this study. Here we show that following UV treatment, p53 levels increased in the OsACL cells despite the presence of high-level endogenous MDM-2; however, CAT assays using a p53 reporter system revealed that this P53 was transcriptionally inactive. Although p53 transactivation was inhibited, MDM-2 levels rose markedly following UV irradiation. Northern blot analysis revealed that the increase in MDM-2 protein levels was a result of increased levels of mdm-2 mRNA, possibly due to increased transcription. Cell cycle analysis revealed that OsACL cells were markedly resistant to UV-induced apoptosis. Transfection of OsACL cells with an anti-sense mdm-2 plasmid dowregulated MDM-2 expression and increased UV-induced apoptosis. In conclusion, MDM-2 overexpression can block UV-induced cell cycle arrest and apoptosis by inhibiting p53 transcriptional activity. Furthermore, increased expression of MDM-2 in OsACL cells following UV irradiation appears to be related to p53-independent mechanisms. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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