Endocrine Abstracts

The pituitary tumor-transforming gene-binding factor (PBF) is a relatively uncharacterised proto-oncogene, which is overexpressed in thyroid tumours. PBF elicits tumor growth in nude mice, whilst thyroid targeted transgenic overexpression in the PBF-Tg mouse induces hyperplasia and macrofollicular lesions, accompanied by induction of the E2 ubiquitin ligase Rad6. Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by c...

Pituitary tumor transforming gene (PTTG) binding factor (PBF) is a proto-oncogene which is frequently upregulated in endocrine cancers. PBF has previously been determined to contain several putative signal sequences within its 180 amino acids. Previous studies have shown the nuclear localisation signal (NLS) to be functional and prediction software now suggests the presence of a putative leucine-rich nuclear export signal (NES) between residues 17 and 27. PBF is known to shutt...

p53 is rarely mutated in thyroid papillary carcinomas, despite the thyroid being highly sensitive to ionising radiation. The pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene overexpressed in thyroid cancer. Oncogenic levels of PBF result in cell transformation in vitro and tumourigenesis in vivo. By serendipity we have found that PBF interacts directly with the tumour suppressor protein p53. In light of these data we have investigated th...

The human pituitary tumor transforming gene is overexpressed in thyroid cancers; inducing genetic instability through its role as a securin and propagating growth through induction of growth factors. We have demonstrated reduced cellular proliferation following hPTTG overexpression in neuronal cells. We hypothesised targeted hPTTG overexpression in mouse thyroids will result in hyperplastic/neoplastic growth and that stimulation of thyroid cell growth through standard methods ...

PTTG is a multifunctional proto-oncogene overexpressed in thyroid cancers, which binds to p53 and modulates its function. PBF, a binding partner of PTTG, is also overexpressed in thyroid cancer and can transform cells independently of PTTG. Moreover, subcutaneous expression of PBF elicits large tumours in nude mice. Given the established role of ionising radiation in thyroid tumourigenesis, we investigated the relationship between PBF and the tumour suppressor protein p53. PBF...

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 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...

The key mitotic regulator pituitary tumor transforming gene (PTTG) is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We examined the function and expression of PTTG’s interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with PTTG. In contrast to PTTG, the cleaved forms of separase and Rad21 were hi...

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=...