Endocrine Abstracts

We have previously shown PTTG and PBF to be over-expressed in differentiated thyroid cancer and to be prognostic indicators for recurrence. Subsequently we reported PBF to be a transforming gene in vitro and tumourigenic in vivo. Since over-expression of PTTG results in the same findings, we examined whether PBF-induced tumourigenesis was an independent effect, or else a result of increased PTTG activity. Two HA-tagged mutants of PBF were generated, firstly subst...

Thyroid hormones play a major role in the metabolic function of mammalian cells and are of particular importance in the development of the fetal brain. The MCT8 gene has recently been shown to encode an active and specific thyroid hormone transporter. Recent reports have identified mutations in the MCT8 gene in several unrelated boys presenting with severe X-linked psychomotor retardation and elevated serum T3.Ontogeny of mRNA encoding MCT8 was examined ...

Objectives: Glucose insulin potassium (GIK) improves haemodynamic performance following coronary artery bypass graft surgery (CABG). We postulated that this might be secondary to beta-1 adrenergic receptor (ADRB1) up-regulation and changes in myocyte calcium handling.Methods: We performed a randomised double-blind placebo-controlled trial on patients undergoing first time elective/urgent on-pump CABG (LREC approval obtained). A cohort of 48 patients rand...

VEGF exerts its effects by binding to two tyrosine kinase receptors, KDR and VEGFR1. KDR is critical for transmitting signals for proliferation and migration of endothelial cells but is also expressed in several non-endothelial cells, and is elevated in some human tumour cells. We investigated KDR expression in human thyroid epithelial cells in vitro and thyroid cancers compared with normal thyroid samples examined ex vivo. Expression of KDR was demonstrated usin...

During the metaphase to anaphase transition of mitosis, destruction of the human securin, pituitary tumor-transforming gene (PTTG), and subsequent activation of the cysteine endopeptidase separase, leads to the cleavage of RAD21, a component protein of the cohesin complex. The developing fetal brain has rapidly proliferating neuronal cells, whilst adult neurons no longer proliferate and are maintained in G0 status of the cell cycle. We have previously investigated the expressi...

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...

Mutations in the plasma membrane thyroid hormone (TH) transporter, MCT8, are associated with severe global neurological deficits accompanied by abnormal circulating TH levels. We have previously shown that MCT8 over-expression in human neuronal precursor cells (NT2) increases cellular T3 uptake and reduces proliferation.Objectives: To quantify and localise the expression of MCT8 in human fetal CNS and to investigate the role of MCT8 in NT2 neurodifferent...

The sodium iodide symporter (NIS) mediates the uptake of iodide into thyroid follicular cells. The pituitary tumor transforming gene (PTTG) is a multifunctional oncogene which stimulates expression of fibroblast growth factor-2 (FGF-2) via the PTTG binding factor (PBF). PTTG, FGF-2 and PBF are all up-regulated in thyroid cancer. PTTG and FGF-2 inhibit NIS mRNA expression and iodide uptake in rat thyroid FRTL5 cells. We have shown previously that both PTTG and PBF repres...