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Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer

Gene Therapy volume 8, pages 1401–1408 (2001)Cite this article

Abstract

p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via adenoviral vectors, and compared their effects on cell growth. Among 10 cell lines tested, six cell lines displayed a similar response following transduction of p53, p73β or p51A/p63γ; two lines underwent cell-cycle arrest, three lines exhibited apoptosis and one line showed no-effect following transduction. The effect on cell-cycle progression was variable in the other four cell lines. Interestingly, three cell lines were resistant to p53-mediated apoptosis, including two lines having endogenous wild-type p53 alleles, but underwent apoptosis after transduction of p73β or p51A/p63γ. Similar to p53, transduction of p51A/p63γ induced extensive apoptosis when combined with adriamycin or X-radiation in SW480 cells, which are normally resistant to apoptosis. Transduction of p73β and p51A/p63γ also reduced the tumorigenicity of two colorectal cancer cells in vivo. These results suggest that adenovirus-mediated p73β and p51A/p63γ transfer are potential novel approaches for the treatment of human cancers, particularly for tumors that are resistant to p53 gene therapy. Gene Therapy (2001) 8, 1401–1408.

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Acknowledgements

We thank Dr Joseph F Costello for critical comments about this manuscript. This research was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo, 060-8556, Japan

    Y Sasaki, I Morimoto, S Ishida, T Yamashita & T Tokino

  2. First Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo, 060-8556, Japan

    Y Sasaki, I Morimoto & K Imai

  3. Department of Dermatology, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo, 060-8556, Japan

    T Yamashita

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  1. Y Sasaki
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Sasaki, Y., Morimoto, I., Ishida, S. et al. Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer. Gene Ther 8, 1401–1408 (2001). https://doi.org/10.1038/sj.gt.3301538

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