Noninvasive and real-time monitoring of the therapeutic response of tumors in vivo with an optimized hTERT promoter.

Abstract:

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS:Collectively, this technology provides a valuable, noninvasive method to evaluate the real-time therapeutic response of tumors in vivo.

journal_name

Cancer

journal_title

Cancer

authors

Yu ST,Li C,Lü MH,Liang GP,Li N,Tang XD,Wu YY,Shi CM,Chen L,Li CZ,Cao YL,Fang DC,Yang SM

doi

10.1002/cncr.26476

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

1884-93

issue

7

eissn

0008-543X

issn

1097-0142

journal_volume

118

pub_type

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