| RRC ID |
39653
|
| 著者 |
Takeuchi M, Shichinohe T, Senmaru N, Miyamoto M, Fujita H, Takimoto M, Kondo S, Katoh H, Kuzumaki N.
|
| タイトル |
The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice.
|
| ジャーナル |
Gene Ther
|
| 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.
|
| 巻・号 |
7(6)
|
| ページ |
518-26
|
| 公開日 |
2000-3-1
|
| DOI |
10.1038/sj.gt.3301125
|
| PMID |
10757026
|
| MeSH |
Adenoviridae / genetics
Animals
Apoptosis
Carcinoembryonic Antigen / genetics
Cell Line
Gene Expression
Genes, Dominant*
Genes, ras*
Genetic Therapy / methods*
Genetic Vectors / administration & dosage
Humans
Injections
Liver Neoplasms / physiopathology
Liver Neoplasms / secondary*
Liver Neoplasms / therapy*
Male
Mice
Mice, Nude
Mutation
Pancreatic Neoplasms / physiopathology
Pancreatic Neoplasms / therapy*
Reverse Transcriptase Polymerase Chain Reaction
Spleen
|
| IF |
4.128
|
| 引用数 |
36
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
1C3D3(RCB0796) |
