Bioluminescence imaging of vascular endothelial growth factor promoter activity in murine mammary tumorigenesis.
Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis. We generated a transgenic reporter mouse, VEGF-GL, in which an enhanced green fluorescent protein-luciferase fusion protein is expressed under the control of a human VEGF-A promoter. The VEGF-GL mouse exhibited intense bioluminescence throughout the body at 1 week of age. The signals rapidly declined to a relatively low level as the mice grew. The adult VEGF-GL mouse showed restricted bioluminescence to the areas undergoing wound healing. In contrast, the VEGF-GL mice, which were crossed with mouse mammary tumor virus-polyoma virus middle T antigen transgenic mammary tumor mice, exhibited prominent bioluminescence in the tumors, correlating with VEGF transcription. Tumor bioluminescence was observed in the bigenic mice as early as 8 weeks, before tumors were palpable, and the signals increased with tumor growth. In conclusion, the VEGF-GL mouse permits longitudinal and quantitative assessment of VEGF promoter activity in vivo. The model should facilitate understanding of the molecular controls and pathways that regulate VEGF transcription in vivo.
Faley
Shannon L
SL
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
Takahashi
Keiko
K
Crooke
Cornelia E
CE
Beckham
Joshua T
JT
Tomemori
Takuya
T
Shappell
Scott B
SB
Jansen
E Duco
ED
Takahashi
Takamune
T
D000818:Animals; D015153:Blotting, Western; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D008156:Luciferases