Endocrine Abstracts

By exploiting the canonical function of the sodium iodide symporter (NIS) ablative radioiodine therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodine for effective treatment due to the dysregulation of NIS, which can occur through decreased expression and/or reduced plasma membrane localisation. Although NIS localisation at the plasma membrane is critical for radioiodine uptake the mechanism of NIS tr...

Despite extensive genomic profiling a better understanding of the contributory factors that promote aggressive thyroid cancer is urgently needed. The proto-oncogenes PBF and PTTG have been implicated in thyroid cancer but there is a lack of information regarding their co-expression and specific roles in tumour progression. Separate studies have previously indicated that PBF and PTTG may disrupt pathways associated with the tumour suppressor p53 that are central to DNA-damage r...

Metastasis is a multistep process responsible for the majority of endocrine cancer deaths. Central to the ability of cells to move is the recruitment of actin fibres at the periphery of the cell by key proteins, especially the cortical actin binding protein cortactin. A full understanding of cortactin function is required in order to address metastatic cell activity within endocrine cancer. We used IP-MS to discover protein binding partners, and now identify the proto-oncogene...

Functional disruption of the tumour suppressor p53 has a critical role in promoting the development of most cancers. The proto-oncogenes PBF and PTTG1 both regulate p53 activity, but the relative contribution of each gene in influencing p53 function has not been delineated, especially in thyroid cancer where both proto-oncogenes are commonly overexpressed. To better understand the interplay between PTTG1, PBF and p53 in vivo, we examined p53 responses in primary thyrocytes cul...

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 ...

Backgeound and Aims: Phaeochromocytomas (PCC) and paragangliomas (PGL) are mostly benign sympathoadrenal tumours. However, there are no available markers to predict a malignant course. Since hypoxia is involved in the pathogenesis of these tumours, we aimed to qualify the relevance of the mammalian Target of Rapamycin (m-TOR) and hypoxic pathways in benign and malignant PCC/PGL.Methods: Tissue microarray (TMA) blocks were constructed with 80 PCC/PGL, inc...

Background and Aims: Phaeochromocytoma and paragangliomas are neuroendocrine tumours arising from chromaffin cells. These tumours express somatostatin receptors (SSTRs), which has five different main subtypes (SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5). The differential expression of the different receptor subtypes in these tumours has previously been reported with a small series of tumour samples. Our study examined the expression of SSTR subtypes in a larger series of benign and ...

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...