title: Prohibitin is overexpressed in papillary thyroid carcinomas bearing the BRAF(V600E) mutation.
abstract: BACKGROUND
  Prohibitin (PHB) is a multifunctional protein that is localized in different intracellular sites. PHB may exert different roles in tumorigenesis, having either a permissive action on tumor growth or an oncosuppressor role, depending on the cellular context. The objective of this study was to evaluate PHB expression in normal thyroid tissues, thyroid follicular adenomas (FAs), and papillary thyroid carcinomas (PTCs).
  
  
  METHODS
  PHB expression was analyzed by immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Transfections in the BCPAP and TPC-1 thyroid cancer cell lines were used to evaluate the PHB promoter activity.
  
  
  RESULTS
  In terms of protein and mRNA levels, normal tissues from patients with serum thyrotropin (TSH) values >0.8mU/L had PHB levels that were significantly reduced compared to specimens from patients with serum TSH values <0.5mU/L, suggesting that TSH exerts an inhibitory effect on PHB expression. Consistent with this was the finding that the presence of TSH was associated with low PHB levels in normal FRTL5 thyroid cells. Immunohistochemical analysis showed relatively low and high PHB expression in FAs and PTCs, respectively. PHB mRNA and protein overexpression, as assessed by quantitative RT-PCR and Western blot, was noted only in PTCs bearing the BRAF(V600E) mutation. Notably, cell transfection experiments suggested that presence of the BRAF(V600E) mutation may be associated to increase of the PHB promoter activity.
  
  
  CONCLUSIONS
  PHB is overexpressed in PTCs bearing the BRAF(V600E) mutation. We postulate that the presence of the BRAF(V600E) mutation increases PHB promoter activity and therefore potentially mediates effects of this mutation on the behavior of BRAF(V600E) positive PTCs.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzoni
authors.forename: Mariavittoria
authors.initials: M
authors.lastname: Dima
authors.forename: Maria
authors.initials: M
authors.lastname: D'Agostino
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.forename: Dora
authors.initials: D
authors.lastname: Fabbro
authors.forename: Carla Di
authors.initials: CD
authors.lastname: Loreto
authors.forename: Maura
authors.initials: M
authors.lastname: Pandolfi
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
authors.forename: Sonia
authors.initials: S
authors.lastname: Moretti
authors.forename: Marilena
authors.initials: M
authors.lastname: Celano
authors.forename: Rocco
authors.initials: R
authors.lastname: Bruno
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology*; D000091402:Prohibitins; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013972:Thyrotropin / Q000096:biosynthesis
chemical_list: D017931:DNA Primers; C000717328:PHB protein, human; D000091402:Prohibitins; D012333:RNA, Messenger; D012097:Repressor Proteins; D013972:Thyrotropin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf