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...

ea0034p178 | Neoplasia, cancer and late effects | SFEBES2014

Inhibition of radioiodine uptake by PBF in breast cells is consistent with sodium–iodide symporter repression in the thyroid

Poole Vikki Louise , Read Martin , Watkins Rachel , Modasia Bhavika , Ryan Gavin , Boelaert Kristien , Franklyn Jayne , Smith Vicki , McCabe Christopher

Whilst, radioiodine ablation is an effective therapy for many patients with thyroid cancer, a subset of patients are incapable of accumulating sufficient iodide-131 for effective treatment, due to low sodium–iodide symporter (NIS) activity. Previous work has identified that the overexpression of pituitary tumor transforming gene (PTTG) binding factor (PBF) in thyroid cells leads to the redistribution of NIS from the plasma membrane into intracellular vesicles, thereby red...

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...

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...

ea0031p157 | Neoplasia, cancer and late effects | SFEBES2013

Predicted NES in PBF appears to be functional in vitro

Poole Vikki , Smith Vicki , Ryan Gavin , Gilligan Lorna , Seed Robert , Sharma Neil , Read Martin , Boelaert Kristien , McCabe Christopher

Pituitary tumor transforming gene (PTTG) binding factor (PBF) is a proto-oncogene which is frequently upregulated in endocrine cancers. PBF has previously been determined to contain several putative signal sequences within its 180 amino acids. Previous studies have shown the nuclear localisation signal (NLS) to be functional and prediction software now suggests the presence of a putative leucine-rich nuclear export signal (NES) between residues 17 and 27. PBF is known to shutt...

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...

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...

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...