title: Cyclic AMP-response element modulator inhibits the promoter activity of the sodium iodide symporter gene in thyroid cancer cells.
abstract: BACKGROUND
  Comprehension of the regulatory mechanism involved in the sodium iodide symporter (NIS) expression is of great relevance for thyroid cancer. In fact, restoration of NIS expression would be a strategy to treat undifferentiated thyroid cancer. Previous in vitro findings suggest that the cyclic AMP-response element (CRE) modulator (CREM) is involved in control of NIS expression. In this work, we examined the expression of CREM in a series of thyroid cancer tissues and its action on NIS promoter in human thyroid cancer cells.
  
  
  METHODS
  Expression of mRNA levels for CREM, PAX8 and NIS was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 6 normal thyroid tissues, 22 papillary, 12 follicular and 4 anaplastic thyroid cancers. The effect of CREM on transcriptional activity of the NIS promoter was investigated by transient transfection of human thyroid cell lines.
  
  
  RESULTS
  Compared to normal tissues, NIS and PAX8 mRNA levels were significantly reduced in all types of thyroid cancer. As expected, the maximal decrease was detected in anaplastic thyroid cancer. Conversely, CREM mRNA levels were increased in all types of thyroid cancer, reaching statistical significance for follicular and anaplastic thyroid carcinoma (p=0.0157 and 0.0045, respectively). Transfection experiments showed an inhibitory effect of CREM on NIS promoter activity in various thyroid cancer cell lines.
  
  
  CONCLUSIONS
  These data demonstrate that CREM expression is increased in thyroid cancer tissue and may play a role in the downregulation of NIS expression in thyroid cancer acting at the transcriptional level.
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy .
authors.forename: Nadia
authors.initials: N
authors.lastname: Passon
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.forename: Elisa
authors.initials: E
authors.lastname: Lavarone
authors.forename: Elisa
authors.initials: E
authors.lastname: Bregant
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzoni
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Hershman
authors.forename: Mike S
authors.initials: MS
authors.lastname: Fenton
authors.forename: Maria
authors.initials: M
authors.lastname: D'Agostino
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D051786:Cyclic AMP Response Element Modulator / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D027981:Symporters / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000099209:Sodium-Iodide Symporters
chemical_list: D051786:Cyclic AMP Response Element Modulator; D009841:Oligonucleotides; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters