Endocrine Abstracts

Introduction: Germline and somatic inactivating MEN1 variants are associated with a wide range of inherited and sporadic endocrine tumours. MEN1 encodes the tumour suppressor Menin, a ubiquitously expressed scaffold protein, implicated in multiple cellular processes including transcription, epigenetic regulation, and modulation of key signaling pathways. Despite intensive study, the mechanisms leading to endocrine tumorigenesis remain ill-defined, in part ref...

Thyroid tumor progression is dependent on cell motility, a highly complex process that involves the co-ordination of cell adhesion, actin dynamics and signal transduction. The proto-oncogene pituitary tumor-transforming gene (PTTG)-binding factor (PBF/PTTG1IP) is a transmembrane glycoprotein that is overexpressed in thyroid cancer and associated with a poorer prognosis. PBF significantly promotes thyroid cancer cell migration and invasion through phosphorylation at PBF-Y174 by...

The prolactin receptor (PRLR) signals predominantly through the JAK2-STAT5 pathway regulating multiple physiological functions relating to fertility, lactation, and metabolism. Understanding of PRLR signalling is incompletely defined, with progress hampered by a lack of reported disease-associated variants in the genes for the prolactin hormone (PRL) and/or PRLR. To date, two common germline PRLR variants are reported to demonstrate constitutive activity, with one, Ile146Leu, ...

Adrenocortical carcinoma (ACC) is a rare malignancy with limited treatment options and a heterogenous prognosis. The histological diagnosis of ACC is complex and there is increasing interest in identifying and validating new immunohistochemical markers. Delta-like non-canonical Notch ligand 1 (DLK1) is a cleavable single-pass transmembrane protein. In humans, DLK1 is present in many tissues during foetal development, is restricted to progenitor/stem cells in a few adult tissue...

Approximately 40% of phaeochromocytomas and paragangliomas (PPGL) are associated with a germline mutation. These individuals have a lifetime tumour risk and in the case of SDHx germline mutations, there is a risk of multiple tumours and malignancy. We sought to discover plasma metabolites associated with succinate dehydrogenase (SDH) deficiency and tumorigenesis for potential use as predictive and/or prognostic biomarkers. Plasma samples were collected prospectively from a cli...

Background: New drug approaches are urgently needed that enhance radioiodide (RAI) uptake leading to efficient ablation of thyroid cancer, especially in RAI-refractory disease. We recently utilised high-throughput screening and identified FDA-approved compounds that induce sodium iodide symporter (NIS) function to enhance iodide uptake, including the proteasomal/ VCP inhibitor disulfiram. In vivo, disulfiram is rapidly metabolized to diethyldithiocarbamate (DDC), whic...