Endocrine Abstracts

The human pituitary tumor transforming gene is overexpressed in thyroid cancers; inducing genetic instability through its role as a securin and propagating growth through induction of growth factors. We have demonstrated reduced cellular proliferation following hPTTG overexpression in neuronal cells. We hypothesised targeted hPTTG overexpression in mouse thyroids will result in hyperplastic/neoplastic growth and that stimulation of thyroid cell growth through standard methods ...

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<...

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...

The pituitary tumor transforming gene-binding factor (PBF) is a poorly characterised gene that is over expressed in pituitary and thyroid tumours. Recently we showed that subcutaneous expression of PBF elicits tumours in nude mice, and expression correlates with thyroid tumour recurrence in man. Given the established role of ionising radiation in thyroid tumourigenesis we have now investigated the relationship between PBF and the tumour suppressor protein p53. Initially, we de...