Searchable abstracts of presentations at key conferences in endocrinology

ea0065op6.3 | Neuroendocrinology, Pituitary and Neoplasia | SFEBES2019

JQ1 treatment significantly reduces POMC expression and ACTH secretion from the corticotrophinoma cell line, AtT20

Lines Kate E , Filippakopoulos Panagis , Stevenson Mark , Bountra Chas , Thakker Rajesh V

Corticotrophinomas represent >10% of all surgically removed pituitary adenomas, which are the most commonly encountered intracranial neoplasms that are identified in >25% of unselected autopsies and approximately 20% of the population undergoing intracranial imaging. Corticotrophinomas are associated with hypersecretion of adrenocorticotropic hormone (ACTH), which leads to excessive production of glucocorticoids by the adrenal cortex and the resulting hypercortisolemia causes ...

ea0044oc1.6 | Early Career Oral Communications | SFEBES2016

A time controlled β-cell specific mouse model Men1L/L/RIP2-CreER for pancreatic neuroendocrine tumours (NETs)

Vas Nunes Roeland P , Frost Morten , Stevenson Mark , Lines Kate E , Thakker Rajesh V

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by occurrence of parathyroid tumours and neuroendocrine tumours (NETs) of the pancreas and pituitary, which is caused by mutations of the MEN1 gene, encoding menin. Mouse models are important in elucidating mechanisms of MEN1 tumourigenesis and treatments, but the current models have limitations. Thus, in conventional heterozygous MEN1 knockout models, tumour d...

ea0044p123 | Neoplasia, cancer and late effects | SFEBES2016

MicroRNA miR-3156-5p is down-regulated in serum of Multiple Endocrine neoplasia type 1 patients, and regulates expression of mortality factor 4-like protein 2 (MORF4L2)

Lines Kate E , Stokes Victoria , Grozinsky-Glassberg Simona , Yates Christopher J , Thakker Rajesh V

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid tumours, and neuroendocrine tumours (NETs) of the pancreas and pituitary. Reliable biomarkers, ideally in plasma or serum, for the early detection and recurrence of MEN-1 associated tumours, and especially pancreatic NETs are required, and we explored the potential use of microRNAS (miRNAs), which are small non-coding RNAs that bind target mRNAs ...

ea0044p145 | Neuroendocrinology and pituitary | SFEBES2016

The epigenetic modifying compound, JQ1+, increases apoptosis in pituitary tumours

Lines Kate E. , Stevenson Mark , Filippakopoulos Panagis , Muller Susanne , Knapp Stefan , Bountra Chas , Thakker Rajesh V

Epigenetic modifications and chromatin remodelling have been demonstrated to play a key role in the development, and progression of multiple cancers, and compounds regulating these mechanisms represent a novel class of anti-cancer drugs. Menin, which is encoded by the MEN1 gene, whose mutations result in a syndrome characterised by pituitary, parathyroid and pancreatic islet tumours, binds histone modifying enzymes, including the histone methyltransferase MLL1. Furthe...

ea0059oc6.6 | Neuroendocrinology and Reproduction | SFEBES2018

An epigenetic modifier reduces proliferation in pituitary cells and suppresses calcium-sensing receptor signalling

Lines Kate E , Gluck Anna K , Bountra Chas , Thakker Rajesh V , Gorvin Caroline M

JQ1 is a bromodomain inhibitor that specifically targets the BET protein family (comprising Brd2, Brd3, Brd4 and BrdT), which promote the transcription of genes by binding acetylated histone residues and recruiting transcriptional machinery. JQ1 has been shown to have efficacy in the treatment of neuroendocrine tumours, however the genes regulated by the BET family in endocrine tissues, particularly in the pituitary, have not been elucidated. We therefore performed RNA-Seq ana...

ea0059p117 | Neoplasia, cancer & late effects | SFEBES2018

Epigenetic inhibitor treatment reduces proliferation via induction of apoptosis in a human typical bronchial carcinoid cell line

Selberherr Andreas , Lines Kate E , Gronzinsky-Glasberg Simona , Bountra Chas , Thakker Rajesh V

Neuroendocrine tumours (NETs), occurring at multiple sites including the pancreas, lung and pituitary, are increasing in incidence and usually present at an advanced metastatic stage, and current medical treatments have limited efficacy. Epigenetic modifiers are promising new drugs, as mutations in the multiple endocrine neoplasia type 1 (MEN1) gene, encoding the histone methyltransferase MLL1 interacting protein, menin, are known to cause both familial and sporadic N...

ea0038oc2.6 | Translational pathophysiology and therapeutics | SFEBES2015

Treatment with the epigenetic modifying compound JQ1+ can significantly reduce the proliferation of pancreatic neuroendocrine tumours in a mouse model of multiple endocrine neoplasia type 1

Lines Kate E , Stevenson Mark , Filippakopoulos Panagis , Muller Susanne , Knapp Stefan , Bountra Chas , Thakker Rajesh V

There are currently no curative treatments for metastatic pancreatic neuroendocrine tumours (PNETs), and the 5-year survival is <50%. Such tumours frequently have mutations in chromatin remodelling genes as well as the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin, which is mutated in up to 40% of sporadic PNETs, and binds the histone methyltransferase MLL1. Histone modifications, and specifically acetylated residues on histone tail...

ea0038p146 | Neoplasia, cancer and late effects | SFEBES2015

The somatostatin analogue pasireotide decreased proliferation and increased apoptosis in pancreatic and pituitary neuroendocrine tumors in a MEN1 mouse model

Stevenson Mark , Walls Gerard , Soukup Ben , Lines Kate , Grossman Ashley , Schmid Herbert , Thakker Rajesh

Improved therapies for pancreatic and pituitary neuroendocrine tumors (NETs), which may occur in Multiple Endocrine Neoplasia type 1 (MEN1), are needed. We assessed the effects of pasireotide, a somatostatin analogue with high affinity for somatostatin receptors (SSTRs) −1, −2, −3 and −5, in a mouse model of MEN1. Men1+/− mice treated from 12 months of age with 40 μg/g pasireotide (n=71), or phosphate-buffered sal...

ea0038p302 | Pituitary | SFEBES2015

Menin regulates the expression of miR-15a, which is downregulated and inversely correlates with cyclin D1 expression in mouse Men1-associated pituitary tumours

Lines Kate E , Newey Paul J , Yates Chris J , Walls Gerard V , Thakker Rajesh V

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid, pituitary and pancreatic islet tumours, and is due to mutations of the MEN1 gene, which encodes the tumour suppressor protein menin. MicroRNAs (miRNA) are non-coding single stranded RNAs that post-transcriptionally regulate gene expression. Alterations in miRNA expression, including downregulation of two miRNAs, miR-15a and miR-16-1, have been r...

ea0055p33 | Poster Presentations | SFEEU2018

A case of vitamin D-dependent rickets type 2A (VDDR2A), caused by compound-heterozygous mutations in the vitamin D receptor (VDR)

Stokes Victoria , Pagnamenta Alistair , Stevenson Mark , Lines Kate E , Shine Brian , Taylor Jenny , Richardson Tristan , Thakker Rajesh V

Case history: Vitamin D-dependent rickets type 2 (VDDR2) is an autosomal recessive condition caused by resistance to 1,25(OH)2D3, either through vitamin D receptor (VDR) mutations (type A) or abnormal expression of interfering proteins (type B), resulting in hypocalcaemia despite elevated plasma 1,25(OH)2D3 and parathyroid hormone concentrations. We report a proband, born to Caucasian non-consanguineous parents, who presente...