Endocrine Abstracts

Pituitary tumor transforming gene (PTTG) is a multifunctional oncogene implicated in the pathogenesis of pituitary and thyroid tumours. In breast cancer, PTTG expression is a prognostic marker for lymph node invasion and tumour recurrence. PTTG expression is regulated in vitro and in vivo by oestrogen treatment. PTTG binding factor (PBF) is also a transforming gene, and was isolated due to its functional interaction with PTTG. In the current study, we examined PB...

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most differentiated thyroid tumours exhibit reduced iodide uptake, however, and the mechanisms accounting for this remain poorly understood. Pituitary tumor transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We recently reported that PTTG and its binding factor PBF, also a potent transfo...

Pituitary tumor-transforming gene binding factor (PBF) is a ubiquitous glycoprotein which is over-expressed in thyroid, breast and other endocrine cancers, and modulates cellular invasion, radioiodine uptake and thyroid hormone efflux. Papillary thyroid cancer patients with high PBF expression show decreased disease-specific survival compared to those with lower expression. PBF expression has recently been correlated with breast cancer metastasis and colon cancer extra-mural v...

Metastasis is a multistep process responsible for the vast majority of endocrine cancer deaths. We have previously identified the proto-oncogene PBF to be upregulated in differentiated thyroid cancer, and recently PBF expression has been correlated with distant thyroid cancer metastasis at diagnosis. Further, PBF potently induces breast cancer cell invasion in vitro, and our recent in vivo data demonstrate that colorectal tumours with higher PBF protein expre...

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...

Whilst, radioiodine ablation is an effective therapy for many patients with thyroid cancer, a subset of patients are incapable of accumulating sufficient iodide-131 for effective treatment, due to low sodium–iodide symporter (NIS) activity. Previous work has identified that the overexpression of pituitary tumor transforming gene (PTTG) binding factor (PBF) in thyroid cells leads to the redistribution of NIS from the plasma membrane into intracellular vesicles, thereby red...

Thyroid growth and differentiation are regulated by TSH via its receptor (TSHR), whilst growth factors signal in parallel via the MAPK/ERK and PI3K/AKT pathways. Aberrant thyroid growth is largely driven by molecular alterations within these signalling pathways. The proto-oncogene pituitary tumor-transforming gene-binding factor (PBF) is expressed in normal thyroid and upregulated in human goitre and thyroid cancer. High PBF expression is associated with tumour recurrence, dis...

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...

Metastasis is a multistep process responsible for the majority of endocrine cancer deaths. Central to the ability of cells to move is the recruitment of actin fibres at the periphery of the cell by key proteins, especially the cortical actin binding protein cortactin. A full understanding of cortactin function is required in order to address metastatic cell activity within endocrine cancer. We used IP-MS to discover protein binding partners, and now identify the proto-oncogene...

PTTG is a multifunctional proto-oncogene, overexpressed in thyroid, pituitary and other endocrine cancers. PTTG is also implicated in the pathogenesis of head and neck cancer, where high PTTG expression independently correlates with advanced tumour stage and reduced disease-free survival. Recently, abrogation of residue threonine-60 (T60) has been associated with altered PTTG half-life, chromosomal instability and cell invasion. We therefore generated a phospho-specific antibo...