RRC ID |
39560
|
著者 |
Ueda K, Iwahashi M, Nakamori M, Nakamura M, Yamaue H, Tanimura H.
|
タイトル |
Enhanced selective gene expression by adenovirus vector using Cre/loxP regulation system for human carcinoembryonic antigen-producing carcinoma.
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ジャーナル |
Oncology
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Abstract |
Selective gene targeting using the carcinoembryonic antigen (CEA) promoter is useful in gene therapy for gastrointestinal cancer. However, the expression of the CEA promoter is not sufficient. In this study, we tried to enhance CEA promoter activity using the Cre/loxP system. The double infection of CEA-producing cells such as MKN45 and LoVo with AxCEANCre and AxCALNLZ at a total multiplicity of infection (MOI) of 50 achieved 7-fold higher expression level of beta-galactosidase activity than single infection of those cells with AxCEALacZ at 50 MOI. On the other hand, the double infection of CEA-nonproducing cells such as MKN1 and HeLa cells showed a very low expression of beta-galactosidase activity. In the subcutaneous tumor models, the administration of AxCEANCre and AxCALNLZ into the CEA-producing tumor showed stronger expression of the LacZ gene in tumor tissue than that of AxCEALacZ. In the experiment using orthotopic models of CEA-producing gastric cancer, intraperitoneal double administration of AxCEANCre and AxCALNLZ caused evident LacZ gene expression in transplanted gastric tumors, but no LacZ gene expression in the normal stomach or liver. It was confirmed that enhanced tissue-specific gene transduction under control of CEA promoter using the Cre/loxP system was useful not only in vitro, but also in vivo, especially in orthotopic models.
|
巻・号 |
59(3)
|
ページ |
255-65
|
公開日 |
2000-9-1
|
DOI |
10.1159/000012169
|
PII |
12169
|
PMID |
11053994
|
MeSH |
Adenoviridae / genetics*
Animals
Carcinoembryonic Antigen / biosynthesis
Carcinoembryonic Antigen / genetics*
Female
Gene Expression Regulation, Neoplastic*
Gene Expression Regulation, Viral
Gene Targeting
Genetic Therapy
Genetic Vectors
Humans
Integrases / genetics*
Mice
Mice, Inbred BALB C
Mice, Nude
Promoter Regions, Genetic / genetics*
Stomach Neoplasms / genetics
Stomach Neoplasms / immunology
Stomach Neoplasms / therapy
Transcriptional Activation
Tumor Cells, Cultured
Viral Proteins*
Xenograft Model Antitumor Assays
|
IF |
2.642
|
引用数 |
18
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
|