Searchable abstracts of presentations at key conferences in endocrinology

ea0021p222 | Endocrine tumours and neoplasia | SFEBES2009

Parafibromin, a tumour suppressor protein, interacts with transforming acidic-coiled coil protein 3 and kinesin family member 5B

Newey Paul , Bowl Michael , Gergely Fanni , Thakker Rajesh

Parafibromin is a tumour suppressor protein, encoded by the gene responsible for the hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is an autosomal dominant disorder, characterised by parathyroid tumours, ossifyfing fibromas, renal and uterine tumours. Parafibromin is a component of the polymerase-associated factor 1 (PAF1) complex and interacts directly with β-catenin, although these functions do not fully explain its role in tumourigenesis. To further investiga...

ea0021oc3.4 | Young Endocrinologists prize session | SFEBES2009

MicroRNAs, let-7 and miR-302, have an altered expression in Men1-null embryos, consistent with abnormal embryonic development

Bowl Michael , Newey Paul , Reed Anita , Walls Gerard , Baban Dilair , Nesbit Andrew , Thakker Rajesh

The multiple endocrine neoplasia type 1 (MEN1) gene, which when mutated gives rise to parathyroid, pancreatic and pituitary tumours, has been shown to have a role in embryogenesis, as Men1-null mice (Men1−/−) are embryonic lethal by 12.5 days post coitum (dpc). MicroRNAs (miRNAs) are emerging as potent regulators of early mammalian embryogenesis, and we therefore undertook expression profiling of miRNAs in Men1+/+ and M...

ea0021p233 | Growth and development | SFEBES2009

A novel dominant-negative Glial Cells Missing B (GCMB) mutation (Asn502His) is associated with autosomal dominant hypoparathyroidism and results in reduced transactivation activity

Bowl Michael , Mirzcuk Samantha , Fratter Carl , Cranston Treena , Allgrove Jeremy , Brain Caroline , Nesbit Andrew , Thakker Rajesh

Glial cells missing B (GCMB), which is the mammalian homologue of the Drosophila GCM gene, encodes a 506 amino acid parathyroid-specific transcription factor that contains: a DNA-binding domain (residues 21–174); a predicted nuclear localization signal (residues 176–193); an inhibitory domain (residues 258–347); and two transactivation domains (residues 174–263, and residues 428–506). To date only two different GCMB m...

ea0021p305 | Pituitary | SFEBES2009

MicroRNAs, miR-15a and miR-16-1, are implicated in pituitary tumourigenesis via regulation of cyclin D1

Newey Paul , Dyar Rebecca , Nesbit Andrew , Javid Mahsa , Walls Gerard , Reed Anita , Bowl Michael , Thakker Rajesh

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that negatively regulate gene expression through imperfect base pairing to the 3′ untranslated regions (UTRs) of target mRNAs. We have investigated the role of the miR-15a–miR-16-1 cluster in pituitary tumourigenesis, as it functions in other cancers as a tumour suppressor via regulation of the cell-cycle regulator cyclin D1. We have used two approaches: 1) in vitro studies examinin...

ea0013p1 | Bone | SFEBES2007

Characterisation of 25 calcium-sensing receptor mutations in disorders of calcium homeostasis

Christie Paul , Curley Alan , Nesbit M Andrew , Harding Brian , Bowl Michael , Thakker Rajesh

Ligand binding by the calcium-sensing receptor (CaSR), which belongs to family C of the G-protein coupled receptor super-family, activates the phospholipase C-inositol triphosphate pathway and leads to an increase in intracellular calcium. CaSR inactivating mutations result in the hypercalcaemic disorders of familial benign hypocalciuric hypercalcaemia (FBHH) and neonatal severe primary hyperparathyroidism (NSHPT), whilst activating mutations result in the hypocalcaemic disord...

ea0013oc22 | Novartis Basic Endocrinology Award | SFEBES2007

Mice deleted for a Multiple Endocrine Neoplasia Type 1 (MEN1) allele develop pancreatic, pituitary and parathyroid tumours in association with hypercalcaemia

Lemos Manuel , Harding Brian , Bowl Michael , Reed Anita , Tateossian Hilda , Hough Tertius , Fraser William , Cheeseman Michael , Thakker Rajesh

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, pancreas and pituitary. The MEN1 gene, which is located on chromosome 11q13 and encodes a 610 amino acid protein (menin), belongs to the class of tumour suppressors. To investigate the role of menin in tumour suppression, three different mouse models have been generated through targeted disruption of the Men1 gene. ...

ea0013p126 | Growth and development | SFEBES2007

Characterisation of parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) in 3 families with autosomal recessive hypoparathyroidism

Bowl Michael , Mirczuk Samantha , Southam Lorraine , Mughal Zulf , Ryan Fiona , Shaw Nick , Tham Elaine , Hochberg Ze’ev , Tiosano Dov , Loughlin John , Andrew Nesbit M , Thakker Rajesh

GCMB, which is the mammalian homologue of the Drosophila gene Glial cells missing, encodes a 506 amino acid parathyroid-specific transcription factor that contains: a DNA-binding domain at residues 21–174; a predicted nuclear localization signal at residues 176–193; an inhibitory domain at residues 258–347; and two transactivation domains at residues 174–263, and residues 428–506. Mutations of GCMB, which is located on chrom...