S-Space College of Medicine/School of Medicine (의과대학/대학원) Nuclear Medicine (핵의학전공) Journal Papers (저널논문_핵의학전공)
Visualization of endogenous p53-mediated transcription in vivo using sodium iodide symporter
- Kim, Kwang Il; Chung, June-Key; Kang, Joo Hyun; Lee, Yong Jin; Shin, Jae Hoon; Oh, Hyun Jeong; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul
- Issue Date
- American Association for Cancer Research
- Clin Cancer Res. 2005 Jan 1;11(1):123-8.
- Animals; Biological Transport; Blotting, Western; Cell Line, Tumor; DNA, Complementary/metabolism; Dose-Response Relationship, Drug; Doxorubicin/pharmacology; *Gene Expression Regulation, Neoplastic; Genes, Reporter; Genetic Vectors; Gentamicins/pharmacology; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Perchloric Acid/pharmacology; Plasmids/metabolism; Potassium Compounds/pharmacology; Radionuclide Imaging; Reverse Transcriptase Polymerase Chain Reaction; Symporters/*metabolism; Time Factors; *Transcription, Genetic; Transcriptional Activation; Transfection; Tumor Suppressor Protein p53/*metabolism; Up-Regulation
- PURPOSE: To develop a gamma camera imaging method for the determination of endogenous gene expression, we evaluated the expression of endogenous p53 gene using human sodium iodide symporter (hNIS) gene as reporter. EXPERIMENTAL DESIGN: We constructed cis-p53RE-hNIS reporter vector placed under control of an artificial enhancer (p53RE). Moreover, we transfected it into human hepatoma cell line SK-Hep1 by liposome. Geneticin was used for the selection of stable transfectant (SK-Hep1p53NIS). To evaluate the function of hNIS, the inhibition study was examined with 1 mmol/L potassium perchlorate. After treatment of Adriamycin with serial dose for 24 hours, we measured the uptake of 125I and did Western blot analysis to evaluate expression of p53 protein. Tumor xenografts were produced in nude mice by s.c. injection of SK-Hep1p53NIS cells. After 7 days, scintigraphic images of nude mice before and after Adriamycin treatment were obtained using [99mTc]-pertechnetate. RESULTS: In the SK-Hep1p53NIS cells, Adriamycin-treated cells accumulated up to three times higher than did nontreated cells. Potassium perchlorate inhibited completely the uptake of 125I. As Adriamycin dose increased, radioiodide uptake was significantly correlated with activated p53 as well as total p53 protein level. When Adriamycin (2 mg/kg) was treated in the same mice, a significantly higher uptake of [99mTc]-pertechnetate was observed in SK-Hep1p53NIS xenografts compared with nontreated xenografts (P < 0.05, unpaired t test). CONCLUSIONS: These results suggest that p53 expression level can be monitored by NIS gene expression using cis-p53RE-hNIS system in vitro and in vivo.
- 1078-0432 (Print)
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