The first two authors contributed equally to this article.
Noninvasive and real-time monitoring of the therapeutic response of tumors in vivo with an optimized hTERT promoter
Version of Record online: 25 AUG 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 7, pages 1884–1893, 1 April 2012
How to Cite
Yu, S.-T., Li, C., Lü, M.-H., Liang, G.-P., Li, N., Tang, X.-D., Wu, Y.-Y., Shi, C.-M., Chen, L., Li, C.-Z., Cao, Y.-L., Fang, D.-C. and Yang, S.-M. (2012), Noninvasive and real-time monitoring of the therapeutic response of tumors in vivo with an optimized hTERT promoter. Cancer, 118: 1884–1893. doi: 10.1002/cncr.26476
- Issue online: 19 MAR 2012
- Version of Record online: 25 AUG 2011
- Manuscript Accepted: 6 JUL 2011
- Manuscript Revised: 23 JUN 2011
- Manuscript Received: 25 MAR 2011
- molecular imaging;
- human telomerase reverse transcriptase (hTERT);
- gene therapy
Telomerase is commonly recognized as an effective anticancer target. The human telomerase reverse transcriptase (hTERT), the rate-limiting component of telomerase, is expressed in most malignant tumors, but it is not found in most normal somatic cells. Here, we report a real-time and noninvasive method to monitor tumor response to a lentivirus-based hTERT-conditional suicidal gene therapy.
In this study, we constructed a lentivirus system in which an optimized hTERT promoter was used to drive the expression of the cytosine deaminase (CD) gene, one of the suicide genes, and a green fluorescent protein (GFP) reporter gene (pLenti-CD/GFP). The lentivirus was used to infect telomerase-positive or telomerase-negative cell lines. In vitro and in vivo experiments were conducted to analyze the dynamic processes of exogenous gene expression noninvasively in cell culture and living animals in real time via optical imaging.
The lentivirus was able to express the CD gene and GFP in telomerase-positive tumor cells and significantly decrease cell proliferation after the use of prodrug 5-flucytosine. However, it could not express GFP and CD in telomerase-negative cell lines, nor could it induce any suicidal effect in those cells. The in vivo study showed that telomerase-positive tumors can be visualized after intratumor injection of the lentivirus in tumor-bearing nude mice via an optical imaging system. Significant tumor growth suppression was observed in telomerase-positive tumors.
Collectively, this technology provides a valuable, noninvasive method to evaluate the real-time therapeutic response of tumors in vivo. Cancer 2012;. © 2011 American Cancer Society.