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Endocrine Abstracts (2014) 34 S6.3 | DOI: 10.1530/endoabs.34.S6.3

University of Birmingham, Birmingham, UK.

Most of the oncogenic events in thyroid cancer are known, and the pathways which govern thyroid cell proliferation have been exquisitely mapped. However, existing knowledge does not fully explain the genetic complexity of thyroid cancer, or reveal whether tumours are likely to be benign, malignant, or resistant to treatment. Whilst mutations and chromosomal rearrangements are central to the aetiology of DTC, the altered expression of proto-oncogenes and tumour suppressor genes is likely to exert a critical effect on thyroid cell growth and behaviour. One proto-oncogene which appears to have a central role in thyroid cell physiology is the PTTG1-binding factor (PBF). Expression of PBF is elevated in DTC and correlates with early recurrence, whilst patients with high PBF expression show significantly reduced disease-specific survival. The peptide sequence of PBF shares no significant homology with other human proteins, but is highly conserved. A plethora of roles are emerging for PBF in thyroid cells, revealing that PBF binds to several proteins and regulates their subcellular distribution. Via this route, PBF represses the activity of the sodium iodide symporter NIS, which is essential to radioiodine treatment of thyroid cancer, and monocarboxylate transporter 8 (MCT8), which modulates thyroid hormone efflux from the thyroid. Our observations also point to critical roles in the regulation of p53 stability and cell invasion. Further, we have discerned that PBF is phosphorylated and glycosylated in vitro and in vivo in murine and human thyroid cells, implying post-translational modes of regulation. Although classically a proto-oncogene, 13 substitution-missense mutations of PBF have now been reported in tumour samples via the COSMIC database, suggesting PBF may in fact be capable of functioning as an oncogene. To this end, we and others are now beginning to define the roles of PBF in thyroid cell transformation, tumour progression and thyroid cancer treatment.

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