Noninvasive imaging methods that allow the tracking of critical steps in tumorigenesis and cancer progression in mouse models can impact importantly on efforts to understand tumorigenesis and to monitor the efficacy of anticancer drug candidates. Telomerase activation occurs in over 90% of human cancers as well as in mouse cancer models, and has been proposed be a diagnostic marker for cancer. Here, we propose to generate transgenic luciferase reporter mice with mouse and human genomic DNA constructs for monitoring the in vivo TERT expression, the rate-limiting step of telomerase activation. Our primary objective is to test the feasibility of using such reporters as imaging markers to monitor tumor progression in live animals. These reporters can potentially be used to image tumors in a broad spectrum of mouse cancer models and provide a standard platform for pre-clinical anticancer drug evaluation. In addition, direct comparison of mouse and human TERT promoter activities in these transgenic reporter mice may also reveal the molecular mechanisms underlying the different regulation of telomerase expression in mice and humans. Such difference may account for the discrepancies in tumor spectra between some human cancers and their mouse models.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA106470-01A1
Application #
6869349
Study Section
Special Emphasis Panel (ZRG1-CG (01))
Program Officer
Menkens, Anne E
Project Start
2005-01-18
Project End
2006-12-31
Budget Start
2005-01-18
Budget End
2005-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$156,581
Indirect Cost
Name
Pennsylvania State University
Department
Physiology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
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Wang, Shuwen; Zhao, Yuanjun; Leiby, Melanie et al. (2009) A new positive/negative selection scheme for precise BAC recombineering. Mol Biotechnol 42:110-6
Zhao, Yuanjun; Wang, Shuwen; Popova, Evgenya Y et al. (2009) Rearrangement of upstream sequences of the hTERT gene during cellular immortalization. Genes Chromosomes Cancer 48:963-74
Wang, Shuwen; Hu, Chunguang; Zhu, Jiyue (2007) Transcriptional silencing of a novel hTERT reporter locus during in vitro differentiation of mouse embryonic stem cells. Mol Biol Cell 18:669-77