Oncotarget

Research Papers:

Development of replication-competent adenovirus for bladder cancer by controlling adenovirus E1a and E4 gene expression with the survivin promoter

Ho Kyung Seo, Jeong Bin Seo, Jae-Kook Nam, Kyung-Chae Jeong, Seung-Pil Shin Shin, In-Hoo Kim, Sang Don Lee and Sang-Jin Lee _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2014; 5:5615-5623. https://doi.org/10.18632/oncotarget.2151

Metrics: PDF 1495 views  |   HTML 1738 views  |   ?  


Abstract

Ho Kyung Seo1, Jeong Bin Seo2, Jae-Kook Nam3, Kyung-Chae Jeong4, Seung-Pil Shin3, In-Hoo Kim5, Sang Don Lee2 and Sang-Jin Lee3

1 Center for Prostate Cancer, Gyeonggi-do, Biomedical Research Institute, Pusan National University and Research Institute for Convergence of Biomedical Science and Technology, Pusan

2 Pusan National University and Biomedical Research Institute, Pusan National University and Research Institute for Convergence of Biomedical Science and Technology, Pusan

3 Genitourinary Cancer Branch, Research Institute National Cancer Center, Gyeonggi-do, Korea

4 Biomolecular Function Research Branch, Research Institute National Cancer Center, Gyeonggi-do, Korea

5 Molecular Imaging and Therapy Branch, Research Institute National Cancer Center, Gyeonggi-do, Korea

Correspondence:

Sang-Jin Lee, email:

Sang-Don Lee, email:

Keywords: bladder cancer, gene therapy, adenovirus, survivin

Received: April 6, 2014 Accepted: June 29, 2014 Published: June 30, 2014

Abstract

Survivin is a member of the inhibitors of apoptosis protein family. Here, we examined survivin expression and confirmed abundant survivin expression in bladder cancer cells. This expression pattern indicated that the transcriptional regulatory elements that control survivin expression could be utilized to discriminate cancer from normal cells. We therefore generated a novel adenovirus termed Ad5/35E1apsurvivinE4 with the following characteristics: 1) E1A and E4 protein expression was dependent on survivin promoter activity; 2) the green fluorescence protein gene was inserted into the genome under the control of the CMV promoter; 3) most of the E3 sequences were deleted, but the construct was still capable of expressing the adenovirus death protein with potent cytotoxic effects; and 4) the fiber knob was from serotype 35 adenovirus. As expected from the abundant survivin expression observed in bladder cancer cells, Ad5/35E1apsurvivinE4 replicated better in cancer cells than in normal cells by a factor of 106 to 102. Likewise, Ad5/35E1apsurvivinE4 exerted greater cytotoxic effects on all bladder cancer cell lines tested. Importantly, Ad5/35E1apsurvivinE4 inhibited the growth of Ku7-Luc orthotopic xenografts in nude mice. Taken together, Ad5/35E1apsurvivinE4 indicates that the survivin promoter may be utilized for the development of a replication-competent adenovirus to target bladder cancers.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 2151