Cyclin D1 overexpression in thyroid tumours from a radio-contaminated area and its correlation with Pin1 and aberrant beta-catenin expression

J Pathol. 2004 Apr;202(4):446-55. doi: 10.1002/path.1534.


Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling, while prolyl isomerase Pin1 promotes cyclin D1 overexpression directly or through accumulation of beta-catenin in cancer cells. This study aimed to elucidate whether Pin1 was involved in cyclin D1 overexpression and aberrant beta-catenin in thyroid tumourigenesis by examining 14 follicular adenomas (FAa) and 14 papillary thyroid carcinomas (PTCs). All PTCs displayed cyclin D1 overexpression and strong cytoplasmic beta-catenin and/or decreased membrane beta-catenin expression by immunohistochemistry. Overexpression of cyclin D1 mRNA was observed in 45.5% of FAs and 54.5% of PTCs by TaqMan real-time PCR. Pin1 expression was observed in PTC by immunostaining and was confirmed by reverse transcriptase-PCR. There was a strong correlation between cyclin D1 and Pin1/cytoplasmic/membrane beta-catenin expression (p < 0.001), and between Pin1 and cytoplasmic (p < 0.001)/membrane (p = 0.002) beta-catenin expression in thyroid tumours. Mutation of the beta-catenin gene could not be detected in PTC. Western blot analysis demonstrated high levels of cyclin D1 and beta-catenin as well as Pin1 expression in a human PTC cell line possessing wild-type beta-catenin and APC genes. This study suggests that both cyclin D1 overexpression and aberrant beta-catenin expression are of significance in thyroid tumours. Pin1 expression appears to correlate closely with the level of cyclin D1 and aberrant beta-catenin expression in thyroid tumours such as FA and PTC. Pin1 may be an important factor in regulating cyclin D1 and beta-catenin expression during thyroid carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Transformation, Neoplastic
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Cytoskeletal Proteins / metabolism
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neoplasm Proteins / metabolism*
  • Neoplasms, Radiation-Induced / metabolism*
  • Peptidylprolyl Isomerase / metabolism
  • RNA, Messenger / genetics
  • Radioactive Hazard Release
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / metabolism*
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA, Neoplasm
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neoplasm Proteins
  • RNA, Messenger
  • Trans-Activators
  • beta Catenin
  • Cyclin D1
  • PIN1 protein, human
  • Peptidylprolyl Isomerase