Endocrine Abstracts

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).</...

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...

Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Differentiated thyroid cancers exhibit aneuploidy; cytogenetic studies have demonstrated the importance of genetic instability in thyroid cancer development. Pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and over-exp...

PTTG is tumourigenic in vivo and transactivates fibroblast growth factor-2 (FGF-2). We have previously identified expression of PTTG and FGF-2 as potential prognostic indicators for differentiated thyroid cancer. Critical to PTTG function is a double PXXP motif, forming a putative SH3-interacting domain. We employed cDNA array approaches to identify further genes regulated via this region. MCF12A cells were transiently transfected with vector-only (VO) control, wild-type (WT)-...

Human securin, also known as pituitary tumor transforming gene, plays a critical role during cell division. Ubiquitination of securin during the metaphase to anaphase transition releases its binding partner separase, which cleaves the cohesins holding sister chromatids together. We recently demonstrated reduced securin expression in human fetal versus adult brain, and dissected its role in affecting the proliferation of human embryonal CNS precursor NTERA-2 (NT-2) cells. We ha...

Human securin, known also as pituitary tumor transforming gene (PTTG), has established oncogenic and cell regulatory functions. PTTG transforms cells in vitro, inhibits sister chromatid separation and regulates secretion of fibroblast growth factor-2 (FGF-2). FGF-2 is a key regulator of CNS development and PTTG/securin expression has previously been reported in murine fetal brain. We examined mRNA and protein expression of PTTG and FGF-2 in 35 first trimester (7-12 weeks) and ...

PTTG transforms cells in vitro, is tumourigenic in vivo and regulates secretion of fibroblast growth factor-2 (FGF-2). Critical to transactivation of FGF-2 is PTTG's SH3 interacting domain which encodes the gene's sole phosphorylation site. We explored the mechanisms through which PTTG stimulates FGF-2 expression and cell transformation using specific mutations resulting in unphosphorylated PTTG (phos-), a mimic of constitutive phosphorylation (phos+), and a disr...

Pituitary tumourigenesis is a complex and poorly understood process. Crucial to the initiation and growth of such tumours is the oncogene PTTG, which stimulates FGF-2-mediated angiogenesis. We recently investigated expression of the angiogenic factor VEGF and its receptor KDR in 103 pituitary tumours. Non-functioning tumours demonstrated markedly raised VEGF mRNA (3.2-fold, P<0.05) and protein levels compared to normal pituitaries (N=10). KDR was also highly induced in NFTs...

PTTG has a dual role in tumorigenesis. Firstly, it regulates expression of basic fibroblast growth factor (FGF-2), and secondly, as a human securin homologue, it inhibits sister chromatid separation in mitosis. Securins must be degraded at Destruction Box (DB) motifs by an anaphase promoting complex (APC), before cell division can proceed. We have used a variety of approaches to examine the precise roles of the PTTG Destruction Box and FGF-2 stimulation in cell transformation....

By exploiting the canonical function of the sodium iodide symporter (NIS), ablative radioiodide therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodide due to decreased expression and/or plasma membrane localisation of NIS. Radioiodide therapy has been proposed as a viable treatment for breast cancer, but is hampered by low levels of NIS membrane localisation. Currently, the regulation of NIS trafficki...