Endocrine Abstracts

Whilst the majority of differentiated thyroid cancers (DTC) have oncogenic mutations, a significant minority may be driven by the overexpression of proto-oncogenes. PTTG and PBF are proto-oncogenes which are induced in DTC, elicit tumours in xenograft models and interact in vitro, where PBF shuttles PTTG into the nucleus. However, the relative contributions of each gene to DTC has not been delineated. Here, we constructed a bi-transgenic murine model over-expressing b...

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...

The clinical effectiveness of ablative radioiodine treatment is limited by the ability of the sodium iodide symporter (NIS) to uptake 131I. A significant proportion of well-differentiated thyroid tumours are unable to concentrate sufficient radioiodine for effective therapy, and in other tumour models such as breast, where radioiodine uptake would be an attractive therapeutic option, uptake is insufficient. Pituitary tumor-transforming gene-binding factor (PBF/ PTTG...

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 Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by c...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

Functional disruption of the tumour suppressor p53 has a critical role in promoting the development of most cancers. The proto-oncogenes PBF and PTTG1 both regulate p53 activity, but the relative contribution of each gene in influencing p53 function has not been delineated, especially in thyroid cancer where both proto-oncogenes are commonly overexpressed. To better understand the interplay between PTTG1, PBF and p53 in vivo, we examined p53 responses in primary thyrocytes cul...

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...