Endocrine Abstracts

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...

Disruption of DNA damage response pathways results in an accumulation of genetic mutations, gene amplifications and chromosome alterations, which are key initiating factors in cellular transformation and oncogenesis. PBF is a multifunctional proto-oncogene which is overexpressed in thyroid, pituitary and breast cancers, with roles in cell transformation, invasion and transporter regulation. Recently, we reported that targeted transgenic expression of PBF promotes genetic insta...

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 Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by c...

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...

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...

By exploiting the canonical function of the sodium iodide symporter (NIS) ablative radioiodine therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodine for effective treatment due to the dysregulation of NIS, which can occur through decreased expression and/or reduced plasma membrane localisation. Although NIS localisation at the plasma membrane is critical for radioiodine uptake the mechanism of NIS tr...

Despite extensive genomic profiling a better understanding of the contributory factors that promote aggressive thyroid cancer is urgently needed. The proto-oncogenes PBF and PTTG have been implicated in thyroid cancer but there is a lack of information regarding their co-expression and specific roles in tumour progression. Separate studies have previously indicated that PBF and PTTG may disrupt pathways associated with the tumour suppressor p53 that are central to DNA-damage r...

PBF is a multifunctional proto-oncogene overexpressed in thyroid and other endocrine cancers. Previously we identified a functional interaction between PBF and the tumour suppressor p53 in well-differentiated thyroid cancer (WDTC). Here, we delineate the oncogenic mechanisms of PBF, along with its binding partner PTTG, in head and neck cancer (HNSCC), in which TP53 mutations (mutTP53) are common (>50%). HNSCC tissue revealed significant upregulation of PBF and PTTG mRNA (&...

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...