title: [All-trans retinoic acid improves iodine uptake of thyroid cancer cells via repressing transcriptional activity of β-catenin].
abstract: OBJECTIVE
  To determine whether all-trans retinoic acid (ATRA) could improve iodine uptake via repressing transcriptional activity of β-catenin in thyroid cancer cells.
  
  
  METHODS
  Three kinds of treatment models were firstly established with alcohol, ATRA, and transfection of β-catenin shRNA in undifferentiated human thyroid cancer cell line-SW1736.Then the expressions of sodium iodide symporter (NIS), β-catenin and its regulating factors, epithelial-mensechymal transition (EMT)-phenotype, invasion and metastasis associated proteins were further measured in above three cell models.After that, the influence of ATRA on the functional expression of NIS, iodine uptake potency, tumor growth curve and treatment effect inducing by radioactive iodine was comparatively analyzed in vitro and in vivo trials.
  
  
  RESULTS
  After treated with ATRA, transcriptional activity of β-catenin decreased by downregulating phosphorylation of β-catenin Ser45, Y654 and GSK-3β Ser9. Additionally, ATRA effectively upregulated the protein level of NIS, and reversed EMT phenotype in alcohol treated cells, with absence in epithelial expression of E-cadherin and cytokeratin 18, as well as abnormal expression of Vimentin, urinary plasminogen activator (uPA), uPAR and Fibronectin.Compared with alcohol-treated group, both in vitro proliferation and invasion potential of ATRA treated cells markedly decreased (all P<0.05), and iodine uptake in vitro increased about 3.5-folds (P=0.007). In ATRA-treated animal model, tumor growth potential and tumor mass were significantly inhibited by radio-iodine ((131)I) treatment (all P<0.05).
  
  
  CONCLUSIONS
  ATRA can increase functional expression of NIS via downregulating transcriptional activity of β-catenin and promote isotope sensitivity to radio-iodine in human undifferentiated thyroid cancer.
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, China.
authors.forename: L
authors.initials: L
authors.lastname: Lan
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.forename: H L
authors.initials: HL
authors.lastname: Chen
authors.forename: L L
authors.initials: LL
authors.lastname: Huo
authors.forename: L L
authors.initials: LL
authors.lastname: Deng
authors.forename: G Y
authors.initials: GY
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
mesh_terms: D015153:Blotting, Western; D015820:Cadherins; D045744:Cell Line, Tumor; D006801:Humans; D007455:Iodine; D010766:Phosphorylation; D027981:Symporters; D013964:Thyroid Neoplasms; D014158:Transcription, Genetic; D014212:Tretinoin; D014568:Urokinase-Type Plasminogen Activator; D051176:beta Catenin; D000099209:Sodium-Iodide Symporters
chemical_list: D015820:Cadherins; D007455:Iodine; D027981:Symporters; D014212:Tretinoin; D014568:Urokinase-Type Plasminogen Activator; D051176:beta Catenin; D000099209:Sodium-Iodide Symporters; C495270:CTNNB1 protein, human