Adenovirus expressing mutant p27kip1 enhanced apoptosis and inhibited the growth of xenografted human breast cancer

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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4 Citations (Scopus)

Abstract

Purpose. To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27kip1 (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 p27kip1 induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27kip1 (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 p27kip1 protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27kip1. Thus, the recombinant adenovirus expressing mutant p27kip1 could be useful in gene therapy against breast cancer.

Original languageEnglish
Pages (from-to)1073-1082
Number of pages10
JournalSurgery today
Volume37
Issue number12
DOIs
Publication statusPublished - 2007 Dec

Keywords

  • Adenovirus
  • Breast cancer
  • Mutant
  • p27

ASJC Scopus subject areas

  • Surgery

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    Sasaki, T., Katayose, Y., Yamamoto, K., Mizuma, M., Shiraso, S., Yabuuchi, S., Oda, A., Rikiyama, T., Oikawa, M., Onogawa, T., Suzuki, M., Lee, C. T., & Unno, M. (2007). Adenovirus expressing mutant p27kip1 enhanced apoptosis and inhibited the growth of xenografted human breast cancer. Surgery today, 37(12), 1073-1082. https://doi.org/10.1007/s00595-007-3546-0