title: Enhanced expression of adenovirus-mediated sodium iodide symporter gene in MCF-7 breast cancer cells with retinoic acid treatment.
abstract: Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line.
  
  
  METHODS
  The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans-retinoic acid (ATRA; 10(-8)-10(-6) mol/L).
  
  
  RESULTS
  The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells.
  
  
  CONCLUSIONS
  Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment.
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Lim
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Paeng
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
authors.forename: Dae Hyuk
authors.initials: DH
authors.lastname: Moon
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D018168:Receptors, Retinoic Acid / Q000502:physiology; D047488:Retinoid X Receptors / Q000502:physiology; D027981:Symporters / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D027981:Symporters; D014212:Tretinoin; D000099209:Sodium-Iodide Symporters