Surgery Today

, Volume 37, Issue 12, pp 1073–1082 | Cite as

Adenovirus Expressing Mutant p27 kip1 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
Original Articles

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.

Key words

Adenovirus Mutant p27kip1 Breast cancer 

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Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Tsuyoshi Sasaki
    • 1
  • Yu Katayose
    • 1
  • Kuniharu Yamamoto
    • 1
  • Masamichi Mizuma
    • 1
  • Satoru Shiraso
    • 1
  • Shinichi Yabuuchi
    • 1
  • Akira Oda
    • 1
  • Toshiki Rikiyama
    • 1
  • Masaya Oikawa
    • 1
  • Toru Onogawa
    • 1
  • Masanori Suzuki
    • 2
  • Choon-Taek Lee
    • 3
  • Michiaki Unno
    • 1
  1. 1.Division of Hepato-Biliary Pancreatic Surgery, Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Kamma Memorial HospitalNasushiobaraJapan
  3. 3.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea

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