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Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus.

Authors
Lim, HY; Ahn, M; Chung, HC; Gardner, TA; Kao, C; Lee, SJ; Kim, SJ
Citation
Cancer gene therapy, 11(8):532-538, 2004
Journal Title
Cancer gene therapy
ISSN
0929-19031476-5500
Abstract
Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 protein is highly expressed in uterine cervical cancer tissues, but not in normal cervix, we constructed a tumor-specific replication-competent adenoviral vector utilizing MN/CA9 promoter (Ad-MN/CA9-E1a), which can replicate only in MN/CA9-expressing cells. Infection of Ad-MN/CA9-E1a to MN/CA9-positive uterine cervical cancer cells (HeLa, C-33 A and SiHa) resulted in much stronger Ad5 E1a protein expressions compared with MN/CA9-negative cells (SK-RC-29), suggesting a tissue-specific replication of this recombinant adenovirus. In vitro cytotoxicity assay revealed that the growth of MN/CA9-positive cells was significantly inhibited with 0.01-1 MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC-29) could only be inhibited by as many as 100 MOI. Intratumoral injection of Ad-MN/CA9-E1a effectively induced growth delay of HeLa tumors in nude mice. These results suggest that a novel replication-competent adenoviral vector mediated by MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing tumors with cytotoxic effects and may be utilized for the treatment of uterine cervical cancer.
MeSH terms
Adenoviridae/*geneticsAdenovirus E1A Proteins/biosynthesis/geneticsAnimalsAntigens, Neoplasm/*genetics/metabolismCarbonic Anhydrases/*genetics/metabolismFemaleGene ExpressionGene Therapy/*methodsGenetic Vectors/geneticsHela CellsHumansMicePromoter Regions, Genetic/geneticsRNA, Messenger/analysis/metabolismUterine Cervical Neoplasms/genetics/metabolism/*therapyVirus Replication/geneticsXenograft Model Antitumor Assays
DOI
10.1038/sj.cgt.7700732
PMID
15167900
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Urology
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
AJOU Authors
임, 호영김, 세중
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