title: Human thyroid carcinoma cell lines show different retinoic acid receptor repertoires and retinoid responses.
abstract: OBJECTIVE
  Disturbed expression of retinoic acid (RA) receptors (RAR/RXR) contributes to the pathogenesis and tumor progression of epithelial carcinomas.
  
  
  METHODS
  To examine whether altered responses to retinoids may correlate with differences in RA receptor equipment, retinoid effects were examined in human thyroid carcinoma cell lines of various differentiation stages in culture and after xenotransplantation onto rodent models.
  
  
  METHODS
  Cell growth was assessed by the MTT test, mRNA expression was examined by Northern blot and quantitative competitive RT-PCR, and type I 5'-deiodinase (5'DI) activity was measured by in vitro deiodination assay. Nude rats and mice were used for xenotransplantation experiments.
  
  
  RESULTS
  All-trans-RA and RAR-selective synthetic retinoids stimulated activity and mRNA expression of the thyroid differentiation marker 5'DI in the follicular thyroid carcinoma cell line FTC-133. In the less differentiated FTC-238 cells, stimulation of 5'DI activity was less pronounced than in FTC-133 cells, and a reduced level of RAR beta mRNA was detected. In the anaplastic thyroid carcinoma cell lines HTh 74 and C 643, the activity of 5'DI was not increased by retinoids, and expression of RAR alpha mRNA was reduced. Proliferation of FTC-133 and FTC-238 cells was decreased by all-trans-RA. Pretreatment of FTC-133 with RA resulted in a reduced tumor growth in xenotransplantation experiments as compared with untreated control cells. This reduction was less pronounced in the case of FTC-238 cells. Thus, retinoid therapy might be applied to treat follicular thyroid carcinomas. However, tumor-specific RAR repertoires need to be analyzed as a prerequisite for successful intervention with appropriate, probably receptor-selective retinoids.
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité, Universitätsmedizin Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schmutzler
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: Barbara
authors.initials: B
authors.lastname: Rüger
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011923:Rats, Nude; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D014212:Tretinoin / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000607071:RARA protein, human; D012333:RNA, Messenger; C000607072:Rara protein, mouse; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta; D014212:Tretinoin