Endocrine Abstracts

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...

Chromosomal instability (CIN) is a common feature of many malignancies including papillary and follicular thyroid cancer. During mitosis, there are multiple stages which, if dysregulated, may result in CIN. One critical stage is the regulation of sister-chromatid separation at the metaphase-anaphase transition. Three key protein complexes regulate this process: separase, cohesins and securin (also known as pituitary tumor transforming gene). In vivo, most tumours studied demon...

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 ...

PTTG has been implicated in the pathogenesis of pituitary, thyroid and other tumours. PBF was recently identified as a protein which interacts specifically with PTTG both in vitro and in vivo. PBF facilitates PTTG's nuclear localisation, and mediates its ability to transactivate basic fibroblast growth factor (FGF-2). We investigated PBF expression and function in vitro, and examined its relationship to PTTG action. Transient transfection of wild type PTTG induced a significan...

The critical role of thyroid hormones (TH) in normal human growth and fetal development is well recognised. The availability of tri-iodothyronine (T3) to bind to thyroid hormone receptors is determined by the local concentrations of T3, as well as the local action of deiodinase enzymes that determine conversion of T4.Quantitative real time RT-PCR was used to quantify the expression of mRNAs encoding the specific deiodinase subtypes (D1, D2 & D3) in h...

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...

Pituitary tumor transforming gene binding factor (PBF) is a relatively uncharacterized gene implicated in endocrine neoplasia. Given the presence of putative oestrogen response elements (ERE) in its promoter, we assessed PBF regulation by oestrogen. PBF mRNA expression was induced maximally at 48 h by 20 nM diethylstilbestrol in ERalpha-positive MCF-7 cells (2.1±0.1-fold, P<0.001, N=6). PBF protein expression levels were also significantly up-regulated b...

Radioiodine ablation of differentiated thyroid cancers and their metastases utilises the ability of the thyroid to accumulate iodide. However, most differentiated thyroid tumours exhibit reduced iodide uptake, with the mechanisms underlying this remaining poorly understood. Pituitary tumor transforming gene (PTTG) binding factor (PBF) is a proto-oncogene over-expressed in thyroid tumours, which we have shown to repress sodium iodide symporter (NIS) mRNA expression and inhibit ...

The cohort comprised 2296 patients with Graves’ disease (GD) (1920 females, 376 males) and 361 with Hashimoto’s thyroiditis (HT) (313 females, 48 males) recruited using standard diagnostic criteria for investigation of genetic susceptibility to AITD. We investigated variation in disease phenotype with age and gender, examining factors including biochemical severity, presence of goitre and presence of thyroid eye disease (TED) classified by NOSPECS score.<p class=...

Autoimmune thyroid diseases (AITD), Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) cluster in families. We investigated whether having a family history (FH) of AITD altered age of diagnosis. The cohort comprised 2296 GD (1920F,376M) and 361 HT (313F,48M) recruited according to standard diagnostic criteria. We compared age at diagnosis of GD or HT in those with or without a FH of overt hyper- or hypothyroidism (ascertained using a standardised questionnaire).</...