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Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment

Martin L Read1, Greg D Lewy, Jim C W Fong

  • 1School of Clinical and Experimental Medicine, Institute of Biomedical Research, University of Birmingham, United Kingdom.

Cancer Research
|August 17, 2011
PubMed

Insights

Overexpression of pituitary tumor transforming gene (PTTG)-binding factor (PBF) in mice caused thyroid enlargement and inhibited radioiodide uptake. PBF also drives proliferation in human multinodular goiters.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a proto-oncogene implicated in breast and thyroid tumor development.
  • PBF's role in thyroid pathophysiology remains largely uncharacterized.

Purpose of the Study:

  • To investigate the functional role of PBF in thyroid gland development and function using a murine model.
  • To explore the impact of PBF on thyroid cell proliferation and radioiodide uptake mechanisms.
  • To correlate PBF expression with human thyroid disorders like multinodular goiter (MNG).

Main Methods:

  • Creation of a transgenic mouse model (PBF-Tg) with targeted PBF expression in the thyroid gland.
  • Assessment of thyroid function, histology, and gene expression (NIS, Akt, TSHR, cyclin D1) in PBF-Tg mice.
  • In vitro studies using primary thyroid cell cultures from PBF-Tg mice to evaluate iodide uptake.
  • Analysis of PBF and TSHR expression in human multinodular goiter (MNG) tissues.

Main Results:

  • PBF-Tg mice developed enlarged thyroid glands with hyperplastic and macrofollicular lesions, despite normal thyroid function.
  • Sodium iodide symporter (NIS) expression and iodide uptake were significantly inhibited in PBF-Tg mice.
  • Upregulation of Akt, TSH receptor (TSHR), and cyclin D1 was observed in PBF-Tg thyroids, indicating increased proliferation.
  • Elevated PBF and TSHR levels were found in human MNG tissues compared to normal thyroid tissue.
  • Depletion of PBF in human thyrocytes increased radioiodide uptake.

Conclusions:

  • Overexpression of PBF induces thyroid cell proliferation, hyperplasia, and macrofollicular lesions in mice.
  • PBF inhibits iodide uptake by repressing NIS expression, a critical pathway for radioiodine therapy.
  • PBF and TSHR are upregulated in human MNG, suggesting a role in this hyperproliferative thyroid disorder.
  • PBF represents a potential therapeutic target for managing thyroid hyperplasia and improving radioiodide uptake for treatment.

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