Endocrine Abstracts

The tyrosine kinase receptor, Tie-2, is expressed on endothelial cells where it has a role in angiogenesis in physiological and tumorigenic processes. We have shown that Tie-2 is also expressed on differentiated human thyroid follicular cells, and that its expression is increased in hyperplasia. This study aimed to elucidate the role of the Tie-2 axis in thyroid cells by examining regulation of Tie-2 expression in primary cultures of human thyroid follicular cells and the diff...

A 76-year-old lady developed a tender thyroid swelling following a fall at home. One month later she was admitted with acute dyspnoea, and increased pain and swelling in her neck. She was found to be hyperthyroid on endocrine testing: free T4 (FT4) 24.8 (9-20) picomoles/litre, free T3 (FT3) 8.1 (3.5-6.5) picomoles/litre and thyrotropin (TSH) 0.2 (0.4-5.5) mIU/litre. She also had a raised erythrocyte sedimentation rate (ESR) at 54 mm/hr. She was commenced on hydrocortisone and ...

In vitro human thyroid follicular cells have been shown to secrete vascular endothelial growth factors (VEGFs). VEGFs transduce their effects by binding to their receptors, VEGFRs, leading to receptor phosphorylation and recruitment of downstream signalling molecules. Using RT-PCR we found that normal human thyroid follicular cells in culture express VEGFR-1, VEGFR-2 and VEGFR-3. Western blotting using antisera specific for phosphotyrosine at 1214 of the GRB2 SH2 bindin...

The plasminogen activator (PA) system plays a central role in biological processes that involve extracellular proteolysis including tissue remodelling, blood clotting, angiogenesis and metastases. The thyroid gland is highly vascular and undergoes extensive remodelling in goitre. We found that primary cultures of human thyroid follicular cells secrete large amounts of PAs (2.5-110 U per ml per day per 105 cells), both urokinase-like (uPA) and tissue-type (tPA), and ...

Medullary thyroid cancer (MTC) is rare and mainly sporadic. About ≤25% of cases are inherited from a Ret protooncogene (RET) mutation. >90% of positive mutations develop MTC, either as familial (FMTC), or as part of MEN2. Early detection and treatment of MTC with total thyroidectomy improves prognosis.In 2006, as part of a project to deliver genetics into mainstream medicine, a multidisciplinary clinic (MDC) comprising a specialist thyroid surg...

Connective tissue growth factor (CTGF aka CCN2), is known to be up-regulated by transforming growth factor beta (TGF beta) and plays important roles in cell cycle control, growth, differentiation, cell adhesion, migration, angiogenesis and ECM production. CTGF is overexpressed in fibrotic disease e.g in kidney, lung, heart as well as in tumours. We have examined expression of CTGF in thyroid tissue because TGF beta is known be an autocrine factor, regulated by iodide. Immunohi...

We have recently shown that Tie-2, the receptor for the angiopoietins, is expressed on thyroid follicular cells. This angiogenic receptor was previously thought to be restricted to the endothelium where it influences the maturation of blood vessels. The role of Tie-2 in the growth, function and follicular architecture of thyroid cells is unknown. We have used primary cultures of human thyroid cells and the rat thyroid cell line, FRTL5 to examine the role of this axis. We have ...

Angiogenesis is the rate-limiting step in tumour progression and metastatic spread. Both promoters and inhibitors of angiogenesis have been implicated in thyroid tumourigenesis. We have reported PTTG overexpression in thyroid and other cancers, and PTTG upregulation of the angiogenic factors FGF-2 and VEGF in vitro. To investigate whether PTTG also transactivates other downstream angiogenic effectors, we employed angiogenesis-specific cDNA arrays. Primary thyroid cells and PTT...

The prognosis of differentiated thyroid cancers is influenced by their ability to accumulate iodine and hence their sensitivity to ablative 131I therapy. Radioiodine concentration is mediated by the sodium-iodide symporter (NIS). We have previously identified PTTG and fibroblast growth factor-2 (FGF-2) as potential prognostic indicators for differentiated thyroid cancers. Furthermore, we demonstrated that FGF-2 reduces iodide uptake in FRTL5 cells and primary human ...

Differentiated thyroid cancers are the commonest endocrine malignancies, but there are no reliable molecular markers of prognosis. Pituitary tumor transforming gene (PTTG) plays several potential roles in tumour initiation and progression, including regulating mitosis and stimulating expression of fibroblast growth factor-2 (FGF-2). PTTG expression has been identified as a potential prognostic marker in pituitary adenomas and colon carcinomas. We postulated that PTTG and FGF-2...