Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0031p154 | Neoplasia, cancer and late effects | SFEBES2013

PBF overexpression causes increased p53 ubiquitination and degradation via MDM2

Ryan Gavin , Read Martin , Seed Robert , Smith Vicki , Fong Jim , Turnell Andrew , Franklyn Jayne , McCabe Christopher , Boelaert Kristien

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 Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by c...

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...

ea0015p176 | Endocrine tumours and neoplasia | SFEBES2008

A novel mechanism of thyroid tumorigenesis based on inactivation of p53 by the PTTG-binding factor PBF

Read Martin , Turnell Andy , Kim Dae , Watkins Rachel , Smith Vicki , Fong Jim , Watkinson John , Boelaert Kristien , Franklyn Jayne , McCabe Chris

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 gene p53, a central compone...

ea0044p246 | Thyroid | SFEBES2016

High tumoral expression of PBF and PTTG modulates the DNA damage response and is associated with poor survival in thyroid cancer

Read Martin , Fong Jim , Imruetaicharoenchoke Waraporn , Nieto Hannah , Modasia Bhavika , Fletcher Alice , Thompson Rebecca , Sharma Neil , Bacon Andrea , Watkinson John , Boelaert Kristien , Turnell Andrew , Smith Vicki , McCabe Christopher

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...

ea0038p149 | Neoplasia, cancer and late effects | SFEBES2015

Distinct p53 response profiles in transgenic mouse models of thyroid-specific PBF and PTTG expression

Read Martin , Fong Jim , Imruetaicharoenchoke Waraporn , Modasia Bhavika , Lewy Greg , Ryan Gavin , Sharma Neil , Smith Vicki , Watkinson John , Boelaert Kristien , Turnell Andrew , McCabe Christopher

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...

ea0028oc3.8 | Obesity, thyroid and Addison's disease | SFEBES2012

Dietary factors augment the ability of the proto-oncogene PBF to induce goitrogenesis and hyperplasia in vivo

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

Nodular thyroid disease is common and its pathogenesis remains poorly understood. Previously, we showed that thyroid-targeted overexpression of the proto-oncogene PTTG-Binding Factor (PBF) induced striking thyroid gland enlargement in transgenic mice (PBF-Tg)1. We have now investigated whether dietary factors influence goitrogenesis and the development of hyperplastic lesions in PBF-Tg mice. The mean weight of thyroids (5.8±0.9 mg; n=70) from 7 week old ...

ea0028p334 | Thyroid | SFEBES2012

PBF is a novel regulator of the thyroid hormone transporter MCT8

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

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are important for thyroid hormone (TH) biosynthesis. Initially, sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid and, following biosynthesis, monocarboxylate transporter 8 (MCT8) mediates secretion of TH from the thyroid gland. NIS-mediated radioiodine uptake is also critical in the treatment of thyroid tumours and metastases. We have previously d...

ea0028p338 | Thyroid | SFEBES2012

PBF interacts with cortactin and thyroglobulin in thyroid cells

Sharma Neil , Smith Vicki , Seed Rob , Read Martin , Lewy Gregory , Ryan Gavin , Fong Jim , Kwan Perkin , Watkinson John , Martin Ashley , Boelaert Kristien , Franklyn Jayne , McCabe Chris

PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. Recently, we have shown that PBF binds NIS, MCT8 and p53, but the full spectrum of its interactions and physiological role within the thyroid remain unknown. Previously, we reported a shortlist of potential binding partners elucidated from K1 and TPC1 papillary thyroid carcinoma cells using tandem mass spectrometry (MS/MS, n=4). Here we present validation and characterisation of 2 of these proteins; ...

ea0025oc3.4 | Pituitary and thyroid | SFEBES2011

PTTG promotes mitogenic mechanisms in thyroid cells through autocrine pathways of interaction with growth factors

Lewy Gregory , Ryan Gavin , Stewart Sarah , Read Martin , Smith Vicki , Fong Jim , Warfield Adrian , Eggo Margaret , Seed Robert , Sharma Neil , Kwan Perkin , 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 investigated the pathways of interaction between hPTTG and epidermal growth factor (EGF), transforming growth factor-α (TGF-α), insulin-like growth factor 1 (IGF1) and basic fibroblast growth factor (FGF2) in vitro and in vivo. Synchronised K1 and TPC-1 papillary thyroid...