Endocrine Abstracts

Nodular thyroid disease is common and its pathogenesis remains poorly understood. Previously, we showed that thyroid-targeted overexpression of the proto-oncogene PTTG-Binding Factor (PBF) induced striking thyroid gland enlargement in transgenic mice (PBF-Tg)1. We have now investigated whether dietary factors influence goitrogenesis and the development of hyperplastic lesions in PBF-Tg mice. The mean weight of thyroids (5.8±0.9 mg; n=70) from 7 week old ...

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are important for thyroid hormone (TH) biosynthesis. Initially, sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid and, following biosynthesis, monocarboxylate transporter 8 (MCT8) mediates secretion of TH from the thyroid gland. NIS-mediated radioiodine uptake is also critical in the treatment of thyroid tumours and metastases. We have previously d...

PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. Recently, we have shown that PBF binds NIS, MCT8 and p53, but the full spectrum of its interactions and physiological role within the thyroid remain unknown. Previously, we reported a shortlist of potential binding partners elucidated from K1 and TPC1 papillary thyroid carcinoma cells using tandem mass spectrometry (MS/MS, n=4). Here we present validation and characterisation of 2 of these proteins; ...

The human pituitary tumor transforming gene (hPTTG) is overexpressed in thyroid cancers; it induces genetic instability and propagates growth through the induction of growth factors. We investigated the pathways of interaction between hPTTG and epidermal growth factor (EGF), transforming growth factor-α (TGF-α), insulin-like growth factor 1 (IGF1) and basic fibroblast growth factor (FGF2) in vitro and in vivo. Synchronised K1 and TPC-1 papillary thyroid...

Iodide uptake via the sodium iodide symporter (NIS) is reduced in many thyroid cancers, resulting in poor prognosis following treatment with 131I. The pituitary tumor transforming gene (PTTG) and its binding factor (PBF) are proto-oncogenes implicated in thyroid tumourigenesis and we previously demonstrated PTTG and PBF-induced repression of NIS in vitro. We have recently generated murine transgenic models of targeted overexpression of PBF and PTTG in the thy...

PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. PBF binds to several proteins, including PTTG and NIS, but its full function is unknown. Understanding the range of interactions PBF has within thyroid cells is therefore vital; these were explored by tandem mass spectrometry (MS/MS), which relies on the predictable fragmentation pattern of an amino acid chain to identify the exact proteins present in a sample.K1 and TPC1 papillary th...

The human pituitary tumor transforming gene (hPTTG) plays important roles in tumourigenesis through its function as a securin and by interaction with the tumour suppressor gene p53. We have previously indentified hPTTG expression as a prognostic indicator for differentiated thyroid cancer. We recently generated a transgenic mouse model overexpressing hPTTG targeted to the thyroid gland via a thyroglobulin promoter to delineate PTTG effects on thyroid tumourigenesis in vivo<...

PTTG binding factor (PBF) is a poorly characterised transforming gene that is overexpressed in thyroid tumours and inhibits the activity of the sodium iodide symporter (NIS) in vitro. Our recent investigations demonstrated that PBF mRNA expression was 2.6-fold higher in thyroid tissue excised from patients with multinodular goitres (MNG) than in normal thyroid tissue (n=25, P<0.01). We have now generated a murine transgenic model of targeted overexpres...

The human pituitary tumor transforming gene (hPTTG) is overexpressed in thyroid cancers; it induces genetic instability and propagates growth through the induction of growth factors. We set out to investigate the autocrine and paracrine pathways of interaction between hPTTG and epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and insulin-like growth factor 1 (IGF1) in vitro and in vivo. Synchronised K1 papillary thyroid carcinoma cell...

Ablative therapy for thyroid cancer depends upon the adequate uptake of radioiodine via the sodium iodide symporter (NIS). However, thyroid tumours frequently show reduced iodide uptake, impacting on prognosis. We previously demonstrated that the proto-oncogene PBF binds NIS and modulates its subcellular localisation. We now demonstrate that PBF binds the thyroid hormone transporter MCT8 in GST-pulldown assays, and alters MCT8 subcellular localisation in vitro. To inves...