Endocrine Abstracts

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 gene p53, a central compone...

Background: SSTR substypes are collectively expressed in the majority of NENs. However, SSTR subtype expression is not routinely assessed for clinical decision-making, including patients eligible for targeted radionucleotide therapy. Elucidating the landscape of SSTR subtypes in context of molecular profiles for low-grade (LG-) and high-grade NENs (HG-NENs) provides an opportunity to better tailor targeted therapy. Here, we leverage the ability of transcriptomics to predict NE...

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...

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...

Background: Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1-RA) whose role as a second-line treatment for patients with type 2 diabetes (T2D) has significantly increased. It has demonstrated cardiovascular safety and superiority in terms of glycaemic control and weight loss, compared to other GLP-1-RAs. The most common side effects are mild gastrointestinal, but it may also cause renal failure secondary to dehydration and an increased risk of diabetic retinopa...

Introduction: Pancreatectomy may be necessary to treat hypoglycaemia due to congenital hyperinsulinism (CHI) following failure of medical management. Post-operative complications including infection and persistent hypoglycaemia have been reported after pancreatectomy, but factors predictive of these have not been recognised.Aims: To investigate if early factors or the time to surgery predict risk of CHI surgical complications and hypoglycaemia in the 6 m...

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...