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| Content Provider | Springer Nature Link |
|---|---|
| Author | Ichikawa, Akira Ando, Jiro Suda, Koichi |
| Copyright Year | 2008 |
| Abstract | Treatment of exponentially growing MCF-7 human breast carcinoma cells with tamoxifen (TAM) inhibits cell growth in a dose-dependent manner. However, the molecular basis for the drug’s activity and its relationship to the cell cycle have not yet been clearly established. In this study, we analyzed cell cycle-related proteins used for immunoblotting and flow cytometry in TAM-treated MCF-7 cells. In addition, the ratio of apoptosis in the cell was analyzed using labeling of DNA strand breaks (TdT assay). In flow-cytometric DNA distribution analysis, the S-phase fraction showed a marked decrease and a concomitant increase in G1- and G2-phase cells accompanying the inhibitory effect of TAM; these changes were time- and dose-dependent. Immunoblotting revealed that the levels of p53 and p21$^{WAF1/CIP1}$ in TAM-treated cells increased in a time- and dose-dependent manner, whereas those of p27$^{KIP1}$ and p16 slightly increased or remained unchanged. Furthermore, cyclin D3 and B showed sharp decreases, in contrast with p53 and p21$^{WAF1/CIP1}$ DNA-apoptosis dual analysis using flow cytometry revealed that the TAM-treated samples contained apoptotic cells, the majority of which were arrested in G1 or G2 and showed suppression of Bcl-2 protein. These results suggest that the tumorigenic effect of TAM on MCF-7 cells arises through antitumor effects that are due to the expression of cyclin-dependent kinase inhibitors, especially p21$^{WAF1/CIP1}$ and these are regulated by the decrease of wild-type p53. The proposed mechanism is similar to that underlying the cytotoxic effects of other agents and ionizing irradiation that cause DNA damage. |
| Starting Page | 28 |
| Ending Page | 37 |
| Page Count | 10 |
| File Format | |
| ISSN | 09147470 |
| Journal | Human Cell |
| Volume Number | 21 |
| Issue Number | 2 |
| e-ISSN | 17490774 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2008-01-01 |
| Publisher Place | Tokyo |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | CDK MCF-7 p21 p53 tamoxifen Cell Biology Embryology Oncology Stem Cells Reproductive Medicine Cell Culture |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Cancer Research |
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