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The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic

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Title: The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic
Other Titles: Suppression of metastatic cancer by N116Y
Authors: Takeuchi, M. Browse this author
Shichinohe, T. Browse this author
Senmaru, N. Browse this author
Miyamoto, M. Browse this author
Fujita, H. Browse this author
Takimoto, M. Browse this author
Kondo, S. Browse this author →KAKEN DB
Katoh, H. Browse this author
Kuzumaki, N.8 Browse this author
Authors(alt): 葛巻, 暹8
Keywords: ras suppressor
pancreatic cancer
liver metastasis
Issue Date: Mar-2000
Publisher: Nature Publishing Group
Journal Title: Gene Therapy
Volume: 7
Issue: 6
Start Page: 518
End Page: 526
Abstract: In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and metastasis.1 We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells.2 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 were 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 five 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.
Relation: http://www.nature.com/gt/index.html
Type: article (author version)
URI: http://hdl.handle.net/2115/717
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 葛巻 暹

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