Expression of hedgehog signalling pathway in anaplastic thyroid cancer

Ulrike Hinterseher1, Annette Wunderlich, Silvia Roth

  • 1Department of Visceral, Thoracic- and Vascular Surgery, University Hospital Marburg, Baldingerstrasse, 35043, Marburg, Germany.

Endocrine
|July 18, 2013
PubMed

Insights

The hedgehog signalling pathway is active in anaplastic thyroid cancer (ATC). Inhibiting this pathway with Cyclopamine reduced ATC cell proliferation, suggesting a potential therapeutic target for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The hedgehog signalling pathway plays a role in tumour progression across various cancers.
  • Specific antagonists targeting this pathway offer potential therapeutic strategies.
  • Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options.

Purpose of the Study:

  • To investigate hedgehog pathway component expression in ATC.
  • To determine the effects of the hedgehog inhibitor Cyclopamine on ATC cell lines.

Main Methods:

  • RT-PCR and immunohistochemistry were used to evaluate gene and protein expression of Sonic Hedgehog (SHh), Smoothened (Smo), Patched (Ptc), and Gli-1 in ATC cell lines and tumour specimens.
  • Western blotting analyzed gene product levels.
  • MTT assays assessed cell viability after Cyclopamine treatment.

Main Results:

  • SHh, Smo, Ptc, and Gli were expressed at both mRNA and protein levels in ATC cell lines and tumour samples.
  • Cyclopamine treatment resulted in time- and dose-dependent inhibition of ATC cell proliferation.
  • The IC50 values for Cyclopamine ranged from 1 to 4 μM in both tested cell lines.

Conclusions:

  • The hedgehog pathway is expressed in anaplastic thyroid carcinoma.
  • Inhibition of the hedgehog pathway with Cyclopamine affects ATC cell proliferation.
  • Aberrant hedgehog pathway activation may contribute to the aggressive nature of ATC, warranting further clinical investigation.

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