Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0031oc5.6 | Pituitary and neoplasia | SFEBES2013

Manipulating PBF/PTTG1IP phosphorylation status to improve radioiodine uptake in thyroid and other tumours

Smith Vicki , Sharma Neil , Read Martin , Ryan Gavin , Kwan Perkin , Turnell Andrew , Martin Ashley , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

The clinical effectiveness of ablative radioiodine treatment is limited by the ability of the sodium iodide symporter (NIS) to uptake 131I. A significant proportion of well-differentiated thyroid tumours are unable to concentrate sufficient radioiodine for effective therapy, and in other tumour models such as breast, where radioiodine uptake would be an attractive therapeutic option, uptake is insufficient. Pituitary tumor-transforming gene-binding factor (PBF/ PTTG...

ea0028p141 | Neoplasia, cancer and late effects | SFEBES2012

Oncogenic levels of PBF aberrantly affect p53 function leading to increased genetic instability in thyroid cancer

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

p53 is rarely mutated in thyroid papillary carcinomas, despite the thyroid being highly sensitive to ionising radiation. The pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene overexpressed in thyroid cancer. Oncogenic levels of PBF result in cell transformation in vitro and tumourigenesis in vivo. By serendipity we have found that PBF interacts directly with the tumour suppressor protein p53. In light of these data we have investigated th...

ea0028p340 | Thyroid | SFEBES2012

Targeted hPTTG overexpression in vivo reduces thyroidal growth and thyroid cell proliferation.

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

The human pituitary tumor transforming gene is overexpressed in thyroid cancers; inducing genetic instability through its role as a securin and propagating growth through induction of growth factors. We have demonstrated reduced cellular proliferation following hPTTG overexpression in neuronal cells. We hypothesised targeted hPTTG overexpression in mouse thyroids will result in hyperplastic/neoplastic growth and that stimulation of thyroid cell growth through standard methods ...

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...

ea0038oc5.4 | Thyroid and parathyroid | SFEBES2015

A novel modulator of cellular invasion and metastasis in endocrine cancer

Watkins Rachel , Imruetaicharoenchoke Waraporn , Sharma Neil , Gentillin Erica , Bosseboeuf Emy , Kwan Perkin , Fletcher Rachel , Mehanna Hisham , Boelaert Kristien , Read Martin , Smith Vicki , McCabe Christopher

Metastasis is a multistep process responsible for the majority of endocrine cancer deaths. Central to the ability of cells to move is the recruitment of actin fibres at the periphery of the cell by key proteins, especially the cortical actin binding protein cortactin. A full understanding of cortactin function is required in order to address metastatic cell activity within endocrine cancer. We used IP-MS to discover protein binding partners, and now identify the proto-oncogene...

ea0031p153 | Neoplasia, cancer and late effects | SFEBES2013

Functional induction of the oestrogen-regulated PTTG1-binding factor in colorectal cancer

Kwan Perkin , Read Martin , Seed Robert , Ryan Gavin , Smith Vicki , Watkins Rachel , Lu Wenli , Ward Stephen , Watkinson John , Franklyn Jayne , Boelaert Kristien , McCabe Christopher

PTTG1-binding factor (PBF) is an oestrogen-regulated proto-oncogene that is overexpressed in thyroid, breast and pituitary tumours. The precise role of PBF in tumourigenesis, however, has not been established, nor whether it is also an aetiological factor in non-endocrine cancer. In this study, we investigated PBF function in established colorectal cells and human tumours. Specific binding was evident between the tumour suppressor p53 and both endogenous and exogenous PBF in H...

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; ...