Endocrine Abstracts

Vascular endothelial growth factors (VEGFs) support angiogenesis and thus tissue growth. They are synthesised and secreted by several cell types but their actions are normally limited to endothelial cells which express VEGF receptors (VEGFRs). Using qRT-PCR and Western blotting we found that normal human thyroid follicular cells also express VEGFRs (VEGFR1-3, neuropilin1 and 2). We have examined the regulation of the expression of VEGFs and PlGFs in the cells. Cells were fully...

We have recently shown that human thyroid follicular cells in culture secrete large amounts of active plasminogen activators (PAs). Thyroid cells also secrete large amounts of vascular endothelial growth factors (VEGFs) and express their receptors, the VEGFRs. PAs, as serine proteases, are known to process growth factors, particularly VEGFs into active forms. In endothelial cells, VEGFs stimulate PA production. We examined the effect of inhibiting VEGF signalling on thyroid fo...

We present a 71-year-old gentleman who was referred with a 3-month history of tiredness and proximal myopathy, diarrhoea, rapid weight loss and new onset diabetes mellitus.On examination, he had features consistent with cortisol excess including thin skin, abdominal striae, proximal muscle wasting and peripheral oedema to his thighs. Neck examination revealed a palpable 2-cm right-sided thyroid nodule.Laboratory investigations show...

Temporary hypocalcaemia following total thyroidectomy occurs in around 30% of patients and is usually due to inadvertent damage to the parathyroid glands. Whilst mild cases are easily managed with oral calcium supplementation, there is the potential for severe calcium deficit with the ensuing risks of cardiac dysrhythmias, tetany and in extreme cases death. It is common practice to have a post-surgery protocol to allow the early identification of these patients. Whilst many pr...

Using qRT-PCR, we found that normal human thyroid follicular cells in culture express the mRNAs for the receptors for vascular endothelial growth factors (VEGFRs). qRT-PCR revealed that the relative production of mRNAs for VEGFRs was neuropilin1=neuropilin2=VEGFR2>VEGFR1 >VEGFR3. Western blotting for phosphoVEGFR2 showed labelling of a 235 kDa protein with few degradation products. VEGFR2 is likely in its active, phosphorylated form, because thyroid cells secrete large...

Human thyroid follicular cells in culture synthesise plasminogen activators, both urokinase (uPA) and tissue-type (tPA). The PAs secreted into the culture medium were active (2.5–50 U/ml) and able to mediate the conversion of plasminogen to plasmin. Secreted PA activity (PAA) was markedly increased by epidermal growth factor (EGF) and protein kinase C (PKC) activation with TPA. There was a corresponding increase in uPA and tPA mRNA levels and in uPA and tPA protein secret...

Whilst the majority of familial medullary thyroid cancer (MTC) is caused by germline mutations of the RET proto-oncogene, there are families and individuals with predisposition to MTC in whom no RET mutation has been identified (non-RET MTC). Recently, we identified novel mutations in a single gene termed MTC2 in non-RET MTC individuals by whole exome sequencing. The precise role of these MTC2 germline mutations in MTC tumorigenesis is however unclear. Here, we examined the fu...

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...

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...