title: In vivo imaging of retinoic acid receptor activity using a sodium/iodide symporter and luciferase dual imaging reporter gene.
abstract: 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.
authors.affiliation: Seoul National University College of Medicine, South Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: So
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Shin
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
mesh_terms: 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
chemical_list: D007457:Iodine Radioisotopes; D008156:Luciferases; D018168:Receptors, Retinoic Acid; D027981:Symporters; D013669:Technetium Tc 99m Medronate; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters