Characterization of the insulin-like growth factor axis and Wilms' tumour suppressor gene in hyperparathyroidism

Br J Surg. 2007 Oct;94(10):1232-41. doi: 10.1002/bjs.5566.

Abstract

Background: Genetic mutations and upregulation of growth factors are implicated in the pathogenesis of hyperparathyroidism. The aim of this study was to evaluate the role of Wilms' tumour suppressor gene (WT-1) and the insulin-like growth factor (IGF) axis in hyperparathyroidism.

Methods: The expression of WT-1 and IGF components was examined by immunohistochemistry, reverse transcriptase-polymerase chain reaction and western immunoblotting in a panel of parathyroid specimens from both primary and secondary hyperparathyroidism. A human parathyroid cell culture model was established to examine the parathyroid response to IGF stimulation.

Results: There was a significantly lower level of WT-1 expression in parathyroid tumours than in normal parathyroid glands. Most tumours expressed IGF-I and IGF-II receptors and responded to IGF stimulation. Only IGF-I was present in normal parathyroid glands, whereas IGF-II was expressed exclusively in parathyroid tumours.

Conclusion: Abnormal expression of WT-1 and the IGF axis may play a role in the pathogenesis of hyperparathyroidism.

MeSH terms

  • Cells, Cultured
  • Female
  • Humans
  • Hyperparathyroidism / genetics*
  • Hyperparathyroidism / metabolism
  • Immunohistochemistry
  • Male
  • Mutation / genetics
  • Receptors, Somatomedin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Somatomedins / genetics*
  • Somatomedins / metabolism
  • Up-Regulation
  • WT1 Proteins / genetics*
  • Wilms Tumor / genetics*
  • Wilms Tumor / metabolism

Substances

  • Receptors, Somatomedin
  • Somatomedins
  • WT1 Proteins