Endocrine Abstracts

Hypoxia inducible factor-1alpha (HIF-1α) is a transcription factor regulating expression of many genes related to oxygen homeostasis in response to hypoxic stress. RSUME is a sumoylation enhancer, which was recently cloned from a pituitary cell line with an increased tumorigenic and angiogenic potential. It has been shown that RSMUE is induced by hypoxia and enhances the sumoylation of HIF-1α. Although many studies demonstrated that the level of HIF-1α is remark...

The chemotherapeutic agent temozolomide (TMZ) has been applied for the treatment of pituitary carcinomas, atypical pituitary adenomas and prolactinomas resistant to dopamine agonist treatment with considerable success. Both shrinkage of the tumors and a drop of excessive hormone production were observed in TMZ-responsive patients. In order to clarify whether the TMZ-induced suppression of hormone secretion was a consequence of tumor shrinkage or caused by direct effects on hor...

The tumorigenesis of Cushing’s disease is characterized by somatic mutations in the USP8 gene in almost half of the cases. USP8 encodes for ubiquitin specific protease 8, a deubiquitinase that rescues proteins involved in the regulation of ACTH synthesis in corticotroph cells. In the present study we tested the antisecretory and antiproliferative efficacy of a commercially available specific USP8 inhibitor (IC50 3.1 μM USP8; >90 μM USP7) in immortalized muri...

IntroductionIntegrins are heterodimeric transmembrane proteins composed of alpha and beta subunits that mediate cell-cell and cell-extracellular matrix (ECM) interactions. Several integrins are overexpressed in human cancers and their ECM recognition motif, arginine-glycine-aspartate (RGD), is being utilized for tumour imaging and targeting.AimTo explore the expression and function of RGD-binding integrins in...

IntroductionSomatic USP8 mutations are found in around 50% of Cushing’s disease tumours and are located in a single mutational hotspot that contains the recognition site for 14–3-3. These proteins bind to phosphoserine recognition motifs to alter the function and location of their target proteins, and are deregulated in several cancers. AimTo explore the expression and function of 14–3-3 prot...

IntroductionTP53 mutations have been rarely reported in pituitary tumours. Recently two exploratory exome sequencing studies have identified somatic TP53 mutations in a small number of functional corticotroph tumours (6/18 and 4/10) with USP8 wild type (wt) status, suggesting that they may be more frequent than previously thought. Nevertheless, the clinical impact of those mutations is still unknown.AimTo det...