Searchable abstracts of presentations at key conferences in endocrinology

ea0025oc5.8 | Reproduction and fetal programming | SFEBES2011

Altered fetoplacental growth in monocarboxylate transporter 8 (Mct8) knockout mice

Vasilopoulou Elisavet , Heuer Heike , Trajkovic Marija , Loubiere Laurence , McCabe Christopher , Franklyn Jayne , Kilby Mark , Chan Shiao

The plasma membrane thyroid hormone (TH) transporter, MCT8, is present in the human placenta from early gestation and is postulated to participate in transplacental transfer of TH. In vitro, MCT8 overexpression decreases the survival of human cytotrophoblast in a TH-independent manner.Objective: To examine the role of Mct8 in fetoplacental growth using the Mct8 knockout (ko) mouse model.Methods: Heterozygous females were mat...

ea0021p315 | Reproduction | SFEBES2009

The role of thyroid hormone transporters MCT8 and MCT10 in the EVT-like cell line HTR8-SVneo

Choudhury Juhela , Loubiere Laurence , Vasilopoulou Elisavet , McCabe Christopher , Franklyn Jayne , Kilby Mark , Chan Shiao

Thyroid hormones (THs) are important for fetal and placental development. Monocarboxylate transporters 8 and 10 (MCT8 and MCT10) are effective plasma membrane TH transporters expressed in the human placenta from 6 weeks of gestation. Both have been localized to human villous trophoblasts and extravillous trophoblasts (EVTs).Aims: Using HTR-8/SVneo cells as a model of 1st trimester EVTs, we assessed 1) T3 effects on gene expression, cell prolif...

ea0015p174 | Endocrine tumours and neoplasia | SFEBES2008

A new pathway in the induction of breast cancer

Watkins Rachel , Smith Vicki , Read Martin , Vasilopoulou Elisavet , James Sally , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

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...

ea0015p178 | Endocrine tumours and neoplasia | SFEBES2008

A novel mechanism of NIS repression in differentiated thyroid cancer

Smith Vicki , Read Martin , Watkins Rachel , Turnell Andrew , James Sally , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

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...

ea0015p348 | Thyroid | SFEBES2008

Expression of thyroid hormone transporters in human placenta and changes with intrauterine growth restriction (IUGR)

Chan Shiao , Loubiere Laurence , Vasilopoulou Elisavet , McCabe Christopher , Franklyn Jayne , Kilby Mark

Thyroid hormones (TH) are important for the development of the fetus and placenta. We have previously reported increased placental expression of the potent TH transporter, MCT8, with advancing gestation. The amino acid plasma membrane transporters, MCT10, LAT1, LAT2, and the organic anion transporters, OATP1A2 and OATP4A1, are also known to transport TH.Objective: To describe the ontogeny of these TH transporters and the obligate heterodimer of the LATs,...

ea0013oc34 | British Thyroid Association Award | SFEBES2007

Monocarboxylate transporter 8 (MCT8) represses proliferation of fetal embryonal NT2 and placental JEG-3 cells in vitro

James Sally , McCabe Christopher , Reaves Barbara , Smith Vicki , Chan Shiao , Barrett Timothy , Kilby Mark , Franklyn Jayne

Thyroid hormones play vital roles in fetal brain development. Mutations in MCT8, recently recognised as a specific thyroid hormone transporter, define a novel syndrome of severe X-linked psychomotor retardation and thyroid hormone resistance.N-TERA-2 (NT2) cells (human embryonal cells with characteristics of CNS precursors) were transiently transfected with either WT MCT8 or its L471P, R271H or S448X mutations, described in males affected by severe psych...

ea0077oc2.2 | Endocrine Cancer and Late Effects | SFEBES2021

An emerging role for proteostasis modulators targeting NIS activity to enhance radioiodide therapy in thyroid cancer

Read Martin , Brookes Katie , Thornton Caitlin , Nieto Hannah , Zha Ling , Fletcher Alice , Boelaert Kristien , Smith Vicki , McCabe Christopher

Introduction: New therapeutic strategies are urgently needed to improve radioiodide (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. We recently utilised high throughput screening and identified FDA-approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. Categorisation revealed a high proportion of drugs that modulate proteostasis, with 6 of the top 15 targeting activity of...

ea0059oc2.4 | The best of the best | SFEBES2018

Biochemical analysis of radioiodine uptake enhancement in endocrine cancer

Alshahrani Mohammed , Fletcher Alice , Thornton Caitlin , Brookes Kate , Nieto Hannah , Thompson Rebecca , Read Martin , Boelaert Kristien , McCabe Christopher , Smith Vicki

The most common form of endocrine cancer is differentiated thyroid cancer (DTC). Outcomes of DTC largely depend on radioiodine treatment, which is mediated the sodium-iodide symporter (NIS). However, many tumours exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transform...

ea0038oc5.1 | Thyroid and parathyroid | SFEBES2015

Functional consequences of germline mutations in a novel non-RET medullary thyroid cancer susceptibility gene

Read Martin , Smith Joel , Smith Vicki , Bosseboeuf Emy , Wake Naomi , Watkinson John , Wallis Yvonne , Maher Eamonn , McCabe Christopher , Woodward Emma

Whilst the majority of familial medullary thyroid cancer (MTC) is caused by germline mutations of the RET proto-oncogene, there are families and individuals with predisposition to MTC in whom no RET mutation has been identified (non-RET MTC). Recently, we identified novel mutations in a single gene termed MTC2 in non-RET MTC individuals by whole exome sequencing. The precise role of these MTC2 germline mutations in MTC tumorigenesis is however unclear. Here, we examined the fu...

ea0038oc6.5 | Advances in reproduction and signalling | SFEBES2015

Pituitary tumor transforming gene binding factor (PBF): a novel modulator of iodide uptake and target for Src phosphorylation in breast cancer

Poole Vikki , Fletcher Alice , Modasia Bhavika , Sharma Neil , Thompson Rebecca , Imruetaicharoenchoke Waraporn , Read Martin , Boelaert Kristien , Smith Vicki , McCabe Christopher

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...