Searchable abstracts of presentations at key conferences in endocrinology

ea0063s1.2 | Thyroid in cancer | ECE2019

Iodine refractoriness in thyroid cells

McCabe Chris

The ability of thyroid cells to specifically uptake radioiodine is frequently compromised in the neoplastic setting, particularly in older patients with poorly differentiated thyroid cancer and larger metastases, resulting in a 10-year survival rate of less than 10%. The mechanisms which govern cellular iodide uptake via the sodium iodide symporter (NIS) have been elucidated with increasing molecular clarity over the past 35 years. NIS is regulated in a tissue-specific manner,...

ea0037ew1.3 | Practical publishing advice | ECE2015

Publishing ethics: fabrication, falsification and plagiarism

McCabe Chris

Scientific misconduct is not a question of all or none but presents itself in many shades of grey. It is essential to understand how fabrication, falsification and plagiarism are defined and to be educated where misconduct starts, to what extent it finds its way into today’s science, and what publishers and editors currently do to prevent it....

ea0034s6.3 | Thyroid cell biology comes to your clinic (Supported by <emphasis role="italic">Journal of Molecular Endocrinology</emphasis>) | SFEBES2014

PBF signalling in thyroid tumourigenesis

McCabe Chris

Most of the oncogenic events in thyroid cancer are known, and the pathways which govern thyroid cell proliferation have been exquisitely mapped. However, existing knowledge does not fully explain the genetic complexity of thyroid cancer, or reveal whether tumours are likely to be benign, malignant, or resistant to treatment. Whilst mutations and chromosomal rearrangements are central to the aetiology of DTC, the altered expression of proto-oncogenes and tumour suppressor genes...

ea0021s1.4 | Novel mechanistic insights into thyroid diseases | SFEBES2009

Novel mechanisms regulating the sodium iodide symporter: implications for thyroid tumourigenesis

McCabe Chris

The treatment of thyroid cancer has not changed substantially for several decades, in contrast to most other tumour types. Total thyroidectomy and administration of ablative radioiodine remain the cornerstones of the therapeutic regimen, which is associated with a good 5-year survival rate. Nonetheless, thyroid cancer treatment is not perfect, and several hurdles remain to be overcome. Radioiodine ablation of differentiated thyroid cancers and their metastases utilises the abi...

ea0059p225 | Thyroid | SFEBES2018

Using lightsheet microscopy to explore the relationship between NIS and its functional interactors ARF4, VCP and PBF

Thornton Caitlin , Fletcher Alice , Brookes Katie , Alshahrani Mohammed , Read Martin , Boelaert Kristien , Smith Vicki , McCabe Chris

Effective treatment of differentiated thyroid cancer relies on a multifaceted approach often including administration of 131I to ablate residual cancer cells post-surgery. The success of this treatment hinges upon adequate uptake of iodide by malignant thyroid follicular cells. In a subset of patients, dedifferentiation of the carcinoma can result in aberrant expression and trafficking of the iodide transport protein, the sodium iodide symporter (NIS), resulting in ...

ea0031oc2.3 | Steroids and thyroid | SFEBES2013

A bi-transgenic murine model of PTTG and PBF overexpression in the thyroid gland

Fong Jim , Read Martin , Ryan Gavin , Lewy Greg , Smith Vicki , Boelaert Kristien , Franklyn Jayne , McCabe Chris

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...

ea0013p213 | AMEND Young Investigator's Award | SFEBES2007

The sodium iodide symporter (NIS) is repressed by PTTG via the human NIS upstream enhancer (hNUE)

Smith Vicki , Boelaert Kristien , Stratford Anna , James Sally , Kogai Takahiko , Franklyn Jayne , Mccabe Chris

The sodium iodide symporter (NIS) mediates the uptake of iodide into thyroid follicular cells. The pituitary tumor transforming gene (PTTG) is a multifunctional oncogene which stimulates expression of fibroblast growth factor-2 (FGF-2) via PTTG binding factor (PBF). PTTG and FGF-2 inhibit iodide uptake in rat thyroid FRTL5 cells and PTTG and PBF repress NIS mRNA expression and iodide uptake in primary human thyroid cultures. To determine whether this regulation is a direct tra...

ea0077oc6.4 | Thyroid | SFEBES2021

AP-2 and Moesin Regulate the Internalisation of the Sodium-Iodide Symporter and Affect I125 Uptake in Thyroid Cancer Cells.

Thornton Caitlin , Brookes Kate , Alice Fletcher , Nieto Hannah , Zha Ling , Kocbiyik Merve , Read Martin , Smith Vicki , McCabe Chris

Dysregulation of sodium-iodide symporter (NIS) function is common in differentiated thyroid cancer, resulting in sub-optimal radioiodide therapy and poorer clinical outcome. Recent developments in identifying proteins that regulate the function of the sodium iodide symporter have highlighted two proteins involved in internalisation of NIS from the plasma membrane: AP-2 and moesin. Clathrin-mediated endocytosis (CME) of NIS is facilitated through the adaptor protein 2 (AP2) com...

ea0034oc2.1 | Endocrine regulation of cell behaviour | SFEBES2014

A novel modulator of cell invasion and metastasis

Watkins Rachel , Smith Vicki , Sharna Neil , Read Martin , Kwan Perkin , Fletcher Rachel , Boelaert Kristien , Franklyn Jayne , McCabe Chris

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...

ea0025p195 | Endocrine tumours and neoplasia | SFEBES2011

PBF is induced by ionising radiation and functionally inactivates p53 in thyroid cancer

Seed Robert , Read Martin , Fong Jim , Lewy Greg , Smith Vicki , Kwan Perkin , Ryan Gavin , Boelaert Kristien , Franklyn Jayne , McCabe Chris

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...