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.
| Original language | English |
|---|---|
| Pages (from-to) | 532-538 |
| Number of pages | 7 |
| Journal | Cancer Gene Therapy |
| Volume | 11 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2004 |
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Keywords
- Adenovirus
- Cervix neoplasms
- MN/CA9
- Virus replication
ASJC Scopus subject areas
- Cancer Research
- Genetics
Cite this
Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus. / Lim, Ho Yeong; Ahn, Miwon; Chung, Hyun Cheol; Gardner, Thomas; Kao, Chinghai; Lee, Sang Jin; Kim, Se Joong.
In: Cancer Gene Therapy, Vol. 11, No. 8, 08.2004, p. 532-538.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus
AU - Lim, Ho Yeong
AU - Ahn, Miwon
AU - Chung, Hyun Cheol
AU - Gardner, Thomas
AU - Kao, Chinghai
AU - Lee, Sang Jin
AU - Kim, Se Joong
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Adenovirus
KW - Cervix neoplasms
KW - MN/CA9
KW - Virus replication
UR - http://www.scopus.com/inward/record.url?scp=4043118903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4043118903&partnerID=8YFLogxK
U2 - 10.1038/sj.cgt.7700732
DO - 10.1038/sj.cgt.7700732
M3 - Article
VL - 11
SP - 532
EP - 538
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 8
ER -