title: Expression of cAMP-responsive element binding protein and inducible cAMP early repressor in hyperfunctioning thyroid adenomas.
abstract: OBJECTIVE
  The pathogenesis of thyroid hyperfunctioning adenomas is still only partially understood and controversy exists about the frequency of gain-of-function mutations of the TSH receptor or G(s)alpha gene, which activate the cAMP pathway. The nuclear transcription factors cAMP-responsive element binding protein (CREB) and inducible cAMP early repressor (ICER) are among the final targets of this signalling cascade.
  
  
  METHODS
  In our study we focused on the expression of CREB and ICER genes in the nodular as well as in the extranodular tissue of hyperfunctioning tumours of the thyroid.
  
  
  METHODS
  RT-PCR and Western blot analysis were performed in a series of 14 patients. The presence of an activating mutation of the TSH receptor or of the G(s)alpha gene was ascertained by direct sequencing.
  
  
  RESULTS
  The levels of CREB transcripts did not significantly differ in the adenomas and in the normal tissues (CREB/GAPDH, mean optical density+/-s.e.: 0.98+/-0.18 vs 0.88+/-0.27 respectively, P = not significant (N.S.)), although case-to-case variability was observed. The absence of a significant difference between the adenoma and the surrounding normal tissue was maintained after dividing the patients into two groups, according to TSH receptor status. Accordingly, no significant difference in the levels of CREB protein (total and Ser(133)-phosphorylated) was observed between the nodular and the extranodular tissue. In addition, no difference was found in the levels of ICER transcripts (ICER/GAPDH, mean optical density+/-s.e.: 0.52+/-0.11, nodule vs 0.36+/-0.11, normal thyroid, P=N.S.), independently of the TSH receptor gene status (i.e. wild-type or mutated).
  
  
  CONCLUSIONS
  Our results support the recent hypothesis that the activation of the cAMP pathway in hyperfunctioning adenomas of the thyroid might be counteracted by opposite events and suggest that complex molecular mechanisms might take part in the pathogenesis of hyperfunctioning tumours.
authors.affiliation: Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. a.peri@dfc.unifi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Silvana
authors.initials: S
authors.lastname: Baglioni-Peri
authors.forename: Lisa
authors.initials: L
authors.lastname: Buci
authors.forename: Barbara
authors.initials: B
authors.lastname: Conforti
authors.forename: Federica
authors.initials: F
authors.lastname: Cioppi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Biliotti
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D051697:Activating Transcription Factor 1; D000236:Adenoma / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D011989:Receptors, Thyrotropin / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000097:blood*; D013964:Thyroid Neoplasms / Q000097:blood / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D012097:Repressor Proteins; D013963:Thyroid Hormones; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP