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 Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by c...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...

PTTG1-binding factor (PBF) is an oestrogen-regulated proto-oncogene that is overexpressed in thyroid, breast and pituitary tumours. The precise role of PBF in tumourigenesis, however, has not been established, nor whether it is also an aetiological factor in non-endocrine cancer. In this study, we investigated PBF function in established colorectal cells and human tumours. Specific binding was evident between the tumour suppressor p53 and both endogenous and exogenous PBF in H...

Nodular thyroid disease is common and its pathogenesis remains poorly understood. Previously, we showed that thyroid-targeted overexpression of the proto-oncogene PTTG-Binding Factor (PBF) induced striking thyroid gland enlargement in transgenic mice (PBF-Tg)1. We have now investigated whether dietary factors influence goitrogenesis and the development of hyperplastic lesions in PBF-Tg mice. The mean weight of thyroids (5.8±0.9 mg; n=70) from 7 week old ...

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are important for thyroid hormone (TH) biosynthesis. Initially, sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid and, following biosynthesis, monocarboxylate transporter 8 (MCT8) mediates secretion of TH from the thyroid gland. NIS-mediated radioiodine uptake is also critical in the treatment of thyroid tumours and metastases. We have previously d...

The human pituitary tumor transforming gene (hPTTG) is overexpressed in thyroid cancers; it induces genetic instability and propagates growth through the induction of growth factors. We investigated the pathways of interaction between hPTTG and epidermal growth factor (EGF), transforming growth factor-α (TGF-α), insulin-like growth factor 1 (IGF1) and basic fibroblast growth factor (FGF2) in vitro and in vivo. Synchronised K1 and TPC-1 papillary thyroid...

Iodide uptake via the sodium iodide symporter (NIS) is reduced in many thyroid cancers, resulting in poor prognosis following treatment with 131I. The pituitary tumor transforming gene (PTTG) and its binding factor (PBF) are proto-oncogenes implicated in thyroid tumourigenesis and we previously demonstrated PTTG and PBF-induced repression of NIS in vitro. We have recently generated murine transgenic models of targeted overexpression of PBF and PTTG in the thy...