| Autor: |
Tsuyoshi Sasaki, Yu Katayose, Kuniharu Yamamoto, Masamichi Mizuma, Satoru Shiraso, Shinichi Yabuuchi, Akira Oda, Toshiki Rikiyama, Masaya Oikawa, Toru Onogawa, Masanori Suzuki, Choon-Taek Lee, Michiaki Unno |
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| Zdroj: |
Surgery Today; Dec2007, Vol. 37 Issue 12, p1073-1082, 10p |
| Abstrakt: |
Abstract Purpose To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27 kip1 (Adp27-mt), which consists of a mutation of Thr-187/Pro-188 to Met-187/Ile-188. Methods Using the human breast cancer cell lines, MDA-MB-231, ZR-75-1, and MCF-7, we tested Adp27-mt for cell cycle assay, growth inhibition assay, and TdT-mediated dUTP-biotin nick end labeling in a human breast cancer-grafted severe combined immunodeficiency (SCID) mouse model. Results The mutant p27 kip1 induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27 kip1 (Adp27-wt). Adp27-mt inhibits cell growth significantly; being about 5- and 3.5-fold stronger for IC50 than Adp27-wt in the breast cancer cell lines, MDA-MD-231 and ZR-75-1, respectively. In the human breast cancer-grafted SCID mouse model, Adp27-mt induced tumor regression and antitumor effects significantly better than Adp27-wt. Furthermore, Adp27-mt mainly caused G2/M arrest in the cell cycle progression, whereas Adp27-wt mediated a G1/S arrest 48 h after infection. Conclusion The mutant p27 kip1 protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27 kip1 . Thus, the recombinant adenovirus expressing mutant p27 kip1 could be useful in gene therapy against breast cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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