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  • Acquired Diseases
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The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice

Gene Therapy volume 7, pages 518–526 (2000)Cite this article

Abstract

In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and metastasis. We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells. To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embryonic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which was generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically 5 days after tumor cell inoculation. Thus, N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter-driven adenovirus vector indicating that N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis.

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Acknowledgements

We thank Dr Karl Riabowol for critical reading of the manuscript. This work was supported in part by a Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan.

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Authors and Affiliations

  1. Division of Gene Regulation, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan

    M Takeuchi, M Miyamoto, H Fujita, M Takimoto & N Kuzumaki

  2. 2nd Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan

    M Takeuchi, T Shichinohe, N Senmaru, M Miyamoto, S Kondo & H Katoh

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  1. M Takeuchi
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Takeuchi, M., Shichinohe, T., Senmaru, N. et al. The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice. Gene Ther 7, 518–526 (2000). https://doi.org/10.1038/sj.gt.3301125

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