In vivo imaging of retinoic acid receptor activity using a sodium/iodide symporter and luciferase dual imaging reporter gene.
Retinoic acids are natural derivatives of vitamin A, and play important roles in modulating tumor cell growth by regulating differentiation, thus suggesting the potential use of these derivatives in cancer therapy and prevention. To visualize the intranuclear responses of functional retinoic acid receptors, we have developed a dual-imaging reporter gene system based on the use of sodium/iodide symporter (NIS) and luciferase in cancer cell lines. NIS and luciferase genes were linked with an internal ribosome entry site, and placed under the control of an artificial cis-acting retinoic acid responsive element (pRARE/NL). After retinoic acid treatment, I-125 uptake by pRARE/NL transfected cells was found to have increased by up to about five times that of nontreated cells. The bioluminescence intensity of pRARE/NL transfected cells showed dose-dependency. In vivo luciferase images showed higher intensity in retinoic acid treated SK-RARE/NL tumors, and scintigraphic images of SK-RARE/NL tumors showed increased Tc-99m uptake after retinoic acid treatment. The NIS/luciferase imaging reporter system was sufficiently sensitive to allow the visualization of intranuclear retinoic acid receptor activity. This cis-enhancer imaging reporter system may be useful in vitro and in vivo for the evaluation of retinoic acid responses in such areas as cellular differentiation and chemoprevention.
So
Min Kyung
MK
Seoul National University College of Medicine, South Korea.
Kang
Joo Hyun
JH
Chung
June-Key
JK
Lee
Yong Jin
YJ
Shin
Jae Hoon
JH
Kim
Kwang Il
KI
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Lee
Myung Chul
MC
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes; D008156:Luciferases / Q000032:analysis* / Q000235:genetics; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D018168:Receptors, Retinoic Acid / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D027981:Symporters / Q000032:analysis* / Q000235:genetics; D013669:Technetium Tc 99m Medronate; D014212:Tretinoin / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D008156:Luciferases; D018168:Receptors, Retinoic Acid; D027981:Symporters; D013669:Technetium Tc 99m Medronate; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters