Endocrine Abstracts

Although the sodium iodide symporter (NIS) is expressed in 70–80% of breast cancers, only 20–30% is located at the plasma membrane (PM) and therefore functional. Previous work in thyroid cells leads demonstrated that PBF redistributes NIS from the PM into intracellular vesicles, potently reducing radioiodide uptake. We therefore examined whether increased membranous NIS could facilitate radioiodide therapy for breast cancer. Immunofluorescent microscopy revealed co-l...

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...

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...

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...

In thyroid cancer, a reduction in sodium iodide symporter (NIS) expression at the basolateral plasma membrane (PM) of thyrocytes decreases the efficacy of radioiodine imaging, ablative therapy and treatment of metastases. NIS overexpression in breast cancer has resulted in radioiodine being widely proposed as a novel therapeutic strategy. However, uptake is insufficient for tumour destruction. Augmenting NIS PM localisation represents an important therapeutic strategy for incr...

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...