Endocrine Abstracts

The hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by germline mutations of the dual zinc-finger (ZnF) transcription factor, GATA3. To date, 51 GATA3 mutations have been reported, which can be divided broadly into three structural-functional classes: i) mutations that lead to a loss of DNA binding and involve ZnF2; ii) mutations, usually of ZnF1, that bind DNA but result in reduced DNA binding affinity; and iii) mut...

Mutations of the transcription factor GATA3, which is important for maintaining human breast luminal epithelial cell differentiation and quiescence, have been reported in 17 oestrogen receptor (ER) positive breast cancers, although the functional effects of these mutations have not been studied. We therefore investigated 56 ER-positive breast cancers for GATA3 mutations. The tumours were macrodissected, and immunohistochemistry for GATA3 revealed a strong correlation between E...

Hypoxia is a primary stimulus for angiogenesis, which is important for tumour proliferation and survival. The effects of hypoxia on parathyroid tumour cells, which may be important for parathyroid autotransplantation in patients, are however, not known. We therefore assessed the effects of hypoxia on gene expression in parathyroid adenoma cells from patients with primary hyperparathyoridism. Cell suspensions from human parathyroid adenomas (n=5) were cultured and afte...

Pancreatic neuroendocrine tumours (NETs) are reported to show frequent mutations in chromatin remodelling genes, while pituitary NETS have alterations in histone modification. Histone modifications, and specifically acetylated residues on histone tails are recognised by members of the bromo and extra terminal (BET) protein family, via their bromodomains, causing alterations in the transcription of growth stimulating genes. BET bromodomain inhibitors have been demonstrated to s...

Neuroendocrine tumours (NETs), occurring at multiple sites including the pancreas, gastrointestinal tract, lung, thymus and pituitary, usually present at an advanced metastatic stage, and are increasing in incidence and prevalence as awareness and diagnostic techniques have improved. Treatments for NETs including surgery, drugs (e.g. somatostatin analogues), chemotherapy, radiotherapy and radionuclide therapy, are often not effective and as such additional therapeutic agents a...