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...

ea0034p173 | Neoplasia, cancer and late effects | SFEBES2014

The first reported mutations in the pituitary tumor-transforming gene binding factor

Imruetaicharoenchoke Waraporn , Read Martin , Smith Joel , Smith Vicki , Modasia Bhavika , Poole Vikki , Watkins Rachel , Jayne Franklyn , Boelaert Kristien , McCabe Christopher

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...

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...

ea0034p191 | Neoplasia, cancer and late effects | SFEBES2014

ATR kinase function is modulated by the proto-oncogene PBF

Fan Hui , Gagliano Teresa , Read Martin L , Franklyn Jayne A , Boelaert Kristien , Turnell Andrew S , McCabe Christofer J

Disruption of DNA damage response pathways results in an accumulation of genetic mutations, gene amplifications and chromosome alterations, which are key initiating factors in cellular transformation and oncogenesis. PBF is a multifunctional proto-oncogene which is overexpressed in thyroid, pituitary and breast cancers, with roles in cell transformation, invasion and transporter regulation. Recently, we reported that targeted transgenic expression of PBF promotes genetic insta...

ea0034p394 | Thyroid | SFEBES2014

PBF is a component of the molecular signalling pathways that drive hyperplastic and neoplastic thyroid growth

Smith Vicki , Read Martin , Watkins Rachel , Poole Vikki , Modasia Bhavika , Imruetaicharoenchoke Waraporn , Boelaert Kristien , Franklyn Jayne , McCabe Christopher

Thyroid growth and differentiation are regulated by TSH via its receptor (TSHR), whilst growth factors signal in parallel via the MAPK/ERK and PI3K/AKT pathways. Aberrant thyroid growth is largely driven by molecular alterations within these signalling pathways. The proto-oncogene pituitary tumor-transforming gene-binding factor (PBF) is expressed in normal thyroid and upregulated in human goitre and thyroid cancer. High PBF expression is associated with tumour recurrence, dis...

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...

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...