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  • Title: Adenovirus expressing mutant p27kip1 enhanced apoptosis and inhibited the growth of xenografted human breast cancer.
    Author: Sasaki T, Katayose Y, Yamamoto K, Mizuma M, Shiraso S, Yabuuchi S, Oda A, Rikiyama T, Oikawa M, Onogawa T, Suzuki M, Lee CT, Unno M.
    Journal: Surg Today; 2007; 37(12):1073-82. PubMed ID: 18030569.
    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.
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