Endocrine Abstracts

Osteopontin (OPN) is a matricellular protein highly expressed in cancer cells, which is able to modulate tumorigenesis and metastasis in several malignancies, including follicular cell-derived thyroid cancers (TC). OPN is one of the gene products aberrantly expressed in TC, but the contribution of each OPN isoform (OPNi), named as OPNa, OPNb and OPNc, is currently unknown. This study aims to analyze the expression profile of OPNi in TC tissue samples, correlate its expression ...

Effective treatment of differentiated thyroid cancer relies on a multifaceted approach often including administration of 131I to ablate residual cancer cells post-surgery. The success of this treatment hinges upon adequate uptake of iodide by malignant thyroid follicular cells. In a subset of patients, dedifferentiation of the carcinoma can result in aberrant expression and trafficking of the iodide transport protein, the sodium iodide symporter (NIS), resulting in ...

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) are adrenocortical tumors leading to adrenal Cushing’s syndrome. Recently, our laboratory has identified the first gene predisposing frequently to PBMAH in adults, named ARMC5 (Armadillo Repeat Containing 5)1. The ARMC5-inactivating mutations identified in leucocyte and tumour DNA in PBMAH patients suggest that ARMC5 is a tumour suppressor gene. However, the mechanisms of action of ARMC5 remain unkno...

Introduction: Krüpel-like factor 4 (KLF4) is a zinc-finger-type transcription factor expressed in a range of tissues that plays multiple functions. KLF4 is expressed in neural stem cells and is critical to neuronal differentiation. Recent evidence suggests that KLF4 also plays an important role in the central regulation of energy balance. In vitro studies show that KLF4 is a transcriptional regulator of agouti–related protein (AgRP), essential to the hyperph...

Runx2 and Osterix(Osx) have been known as the master transcription factors for bone formation. However, genes that act downstream of both Runx2 and Osx have not been fully studied. To investigate downstream target genes of Runx2 and Osx, DNA microarray was conducted in calvaria of WT, Runx2ΔC/+, Osx+/−, and Runx2ΔC/+; Osx+/− double heterozygous mice designated WT, Runx2het, Osxhet, and Doub...

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and loss-of-function coding mutations in the CaSR-associated G-protein subunit Gα11 have been reported to cause FHH2 in only two patients to date. The aim of our study was therefore to characterise additional <em...

Background: The insulin receptor (INSR) is alternatively spliced in a developmental and tissue specific manner into two isoforms, IR-A and IR-B. IR-A excludes exon 11 and is widely expressed whereas IR-B includes exon 11 and is expressed in insulin sensitive tissues. The severe short stature disorder 3-M syndrome is caused by mutations in CUL7, OBSL1 and CCDC8 and we have recently associated these proteins with the major mRNA splicing pathways includ...

Background/aims: The transcription factor neurogenin 3 (NGN3) is required for pancreatic islet cell specification from multipotent progenitor cells; yet we have limited understanding of the downstream genetic program it directly initiates. A 3 Mb centromeric region on chromosome 20p contains a number of genes activated downstream of NGN3 including INSM1 and NKX2.2. We proposed that NGN3 alters the expression of other genes within this region as poten...

The parallel increase in the amount of environmental contaminants and in the prevalence of some human diseases has led to a growing interest in understanding how these compounds, so-called endocrine disruptors, may affect human health. In this scenario, the concept that obesity is the result of the interplay of genetic and lifestyle factors has been changing due to the growing evidence that environmental contaminants might alter endocrine function.Organo...

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder which is associated with higher incidence of gallstone disease. ICP symptoms are usually presented in the third trimester of gestation and their severity advances in parallel with the increase in serum sulphated progesterone metabolites (P4-S) in the mother. Liver X receptor α (LXRα) actively participates in the regulation of lipid metabolism functioning as a cholesterol ...