Searchable abstracts of presentations at key conferences in endocrinology

ea0025p198 | Endocrine tumours and neoplasia | SFEBES2011

PTTG and PBF: targets for enhancement of radioiodine uptake in thyroid tumours

Lewy Gregory , Read Martin , Smith Vicki , Jim Fong , Ryan Gavin , Stewart Sarah , Seed Robert , Sharma Neil , Kwan Perkin , Eggo Margaret , Franklyn Jayne , McCabe Christopher , Boelaert Kristien

Iodide uptake via the sodium iodide symporter (NIS) is reduced in many thyroid cancers, resulting in poor prognosis following treatment with 131I. The pituitary tumor transforming gene (PTTG) and its binding factor (PBF) are proto-oncogenes implicated in thyroid tumourigenesis and we previously demonstrated PTTG and PBF-induced repression of NIS in vitro. We have recently generated murine transgenic models of targeted overexpression of PBF and PTTG in the thy...

ea0025p335 | Thyroid | SFEBES2011

The use of tandem mass spectrometry to identify binding partners of PBF in thyroid cells

Sharma Neil , Seed Robert , Read Martin , Smith Vicki , Lewy Gregory , Ryan Gavin , Fong Jim , Kwan Perkin , Boelaert Kristien , Franklyn Jayne , Martin Ashley , McCabe Christopher

PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. PBF binds to several proteins, including PTTG and NIS, but its full function is unknown. Understanding the range of interactions PBF has within thyroid cells is therefore vital; these were explored by tandem mass spectrometry (MS/MS), which relies on the predictable fragmentation pattern of an amino acid chain to identify the exact proteins present in a sample.K1 and TPC1 papillary th...

ea0025p340 | Thyroid | SFEBES2011

Targeted hPTTG overexpression in vivo induces reduced cellular proliferation and p53 stabilisation resulting in decreased thyroid size

Ryan Gavin , Lewy Gregory , Read Martin , Seed Robert , Sharma Neil , Smith Vicki , Fong Jim , Kwan Perkin , Franklyn Jayne , McCabe Christopher , Boelaert Kristien

The human pituitary tumor transforming gene (hPTTG) plays important roles in tumourigenesis through its function as a securin and by interaction with the tumour suppressor gene p53. We have previously indentified hPTTG expression as a prognostic indicator for differentiated thyroid cancer. We recently generated a transgenic mouse model overexpressing hPTTG targeted to the thyroid gland via a thyroglobulin promoter to delineate PTTG effects on thyroid tumourigenesis in vivo<...

ea0021oc5.5 | Steroids and thyroid | SFEBES2009

Akt activation in a murine thyroid goitre model induced by the tumourigenic factor PBF

Read Martin , Lewy Greg , Sharma Neil , Fong Jim , Smith Vicki , Seed Robert , Kwan Perkin , Leadbeater Wendy , Warfield Adrian , Watkinson John , Franklyn Jayne , Boelaert Kristien , McCabe Chris

PTTG binding factor (PBF) is a poorly characterised transforming gene that is overexpressed in thyroid tumours and inhibits the activity of the sodium iodide symporter (NIS) in vitro. Our recent investigations demonstrated that PBF mRNA expression was 2.6-fold higher in thyroid tissue excised from patients with multinodular goitres (MNG) than in normal thyroid tissue (n=25, P<0.01). We have now generated a murine transgenic model of targeted overexpres...

ea0021p124 | Cytokines and growth factors | SFEBES2009

PTTG promotes mitogenic mechanisms in thyroid cells through autocrine pathways of interaction with TGF-α, EGF and IGF1

Lewy Greg , Ryan Gavin , Read Martin , Smith Vicki , Fong Jim , Warfield Adrian , Eggo Margaret , Seed Robert , Sharma Neil , Perkin Kwan , Franklyn Jayne , McCabe Christopher , Boelaert Kristien

The human pituitary tumor transforming gene (hPTTG) is overexpressed in thyroid cancers; it induces genetic instability and propagates growth through the induction of growth factors. We set out to investigate the autocrine and paracrine pathways of interaction between hPTTG and epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and insulin-like growth factor 1 (IGF1) in vitro and in vivo. Synchronised K1 papillary thyroid carcinoma cell...

ea0021p218 | Endocrine tumours and neoplasia | SFEBES2009

The role of PBF in NIS and MCT8 cellular trafficking

Smith Vicki , Read Martin , Watkins Rachel , Lewy Gregory , Fong Jim , Seed Robert , Sharma Neil , Ryan Gavin , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

Ablative therapy for thyroid cancer depends upon the adequate uptake of radioiodine via the sodium iodide symporter (NIS). However, thyroid tumours frequently show reduced iodide uptake, impacting on prognosis. We previously demonstrated that the proto-oncogene PBF binds NIS and modulates its subcellular localisation. We now demonstrate that PBF binds the thyroid hormone transporter MCT8 in GST-pulldown assays, and alters MCT8 subcellular localisation in vitro. To inves...

ea0021p224 | Endocrine tumours and neoplasia | SFEBES2009

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

Seed Robert , Read Martin , Fong Jim , Lewy Gregory , Smith Vicki , Watkins Rachel , Kwan Perkin , Sharma Neil , Ryan Gavin , Franklyn Jayne , Boelaert Kristien , McCabe Christopher

The pituitary tumor transforming gene-binding factor (PBF) is a poorly characterised gene that is over expressed in pituitary and thyroid tumours. Recently we showed that subcutaneous expression of PBF elicits tumours in nude mice, and expression correlates with thyroid tumour recurrence in man. Given the established role of ionising radiation in thyroid tumourigenesis we have now investigated the relationship between PBF and the tumour suppressor protein p53. Initially, we de...

ea0070aep60 | Adrenal and Cardiovascular Endocrinology | ECE2020

16 year-old woman with abdominal paraganglioma secondary to SDHB mutation

Bodoque Cubas Javier , Mena Ribas Elena , Serra Soler Guillermo , Antich Barceló Carlos , Argüelles Jiménez Iñaki , Tofé Povedano Santiago , Codina Marcet Mercedes , García Fernández Honorato , Pereg Macazaga Vicente

Introduction: Catecholamine-secreting tumours derived from the adrenal medulla and the nodes of the autonomic nervous system are known as pheochromocytomas or paragangliomas, respectively. Although their clinical manifestations are similar, their differentiation is important from an epidemiological and prognostic point of view and their possibility of being associated with genetic syndromes.Case report: We present a case of a 16 year old patient, with no...

ea0070aep539 | Endocrine-related Cancer | ECE2020

Involvement of the splicing machinery in the antitumoral actions of metformin in prostate cancer

Montero-Hidalgo Antonio J. , Jiménez-Vacas Juan M. , Herrero-Aguayo Vicente , Sarmento-Cabral André , López Miguel , Castaño Justo P , Gahete Manuel D , Luque Raúl M

Metformin has recently emerged as a potential therapeutic tool for different tumour pathologies, including prostate cancer (PCa)1, one of the leading causes of cancer-deaths in men worldwide. However, the molecular mechanisms underlying the antitumor effects of metformin in PCa are not fully elucidated. In this context, previous reports have suggested a relationship between metformin and the process of alternative splicing in some cell-types. Nevertheless, the poten...

ea0070aep928 | Thyroid | ECE2020

Usefulness of tissular heterogeneity analysis measured by elastography in the characterization of tyroid nodules

Sevillano Jiménez Maria , Ravé García Reyes , Socorro García García Clara , Torres Cuadro Alberto , Asunción Martínez Brocca María , Martín Hernández Tomas

Objectives: To assess whether the degree of heterogeneity of thyroid nodules defined by their elastographic characteristics is related to the cytological diagnosis and ultrasound classification of risk of malignancy.Material and Methods: Observational, prospective study. 101 thyroid nodules were analysed by quantitative elastographic analysis (shear-wave), measuring the stiffness of the lesion by global elastography and its standard deviation (s.d.</...