Endocrine Abstracts

The two regulatory subunits (R1 and R2) of PKA are differentially expressed in several cancer cell lines and studies indicate distinct roles for these subunits in growth control. Recently, mutations of the regulatory subunit 1A of PKA gene have been identified in patients with Carney complex (CNC). The aim of this study was to evaluate the expression of the different PKA regulatory subunits (R1A, R2A, R2B) in adrenocortical tumors not associated with CNC, as well as the effect...

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular thyroid C cells that produce calcitonin, accounting for 5%-10% of thyroid cancers. In all inherited cases of MTC, and in about 40% of sporadic cases, activating mutations of the receptor tyrosine kinase proto-oncogene RET are found. Signaling pathways involved in cell proliferation, survival and motility are triggered by constitutively active RET, but the mechanisms underlying mali...

Somatic mutations in splicing factor 3 subunit B1 (SF3B1) were found in about 20% of PRL-secreting PitNETs. SF3B1 is involved in pre-mRNA splicing and required for assembly of the U2 complex, which is critical for branch site recognition and the early stages of spliceosome assembly. Patients with mutant prolactinomas showed higher PRL levels and shorter progression-free survival compared to wild-type patients. Aims of the present study were: 1) to characterize the genetic prof...

Dopamine receptor type 2 (DRD2) agonists (DA) are the first-choice treatment for prolactin (PRL)-secreting pituitary tumors, but poorly effective in non-functioning (NF)-PitNETs. Along with G protein-dependent signaling, DRD2 also mediates non-canonical beta-arrestin-dependent pathways, where reduction of AKT phosphorylation plays a leading role for the antiproliferative effect of DRD2 in pituitary tumors. Through UNC9994 and MLS1547, a beta-arrestin 2-biased and a G protein-b...

Adrenocortical carcinomas (ACCs) are rare endocrine tumors with poor prognosis. They overexpress the insulin-like growth factor 2 (IGF2), that drives a proliferative autocrine loop by binding to IGF1R and IR. The majority of studies focused on IGF1R as mediator of IGF2 biological effects, but recently a high expression of IR, in particular of the isoform A, was observed in most ACCs, suggesting a potential role of this receptor in modulating IGF2 effects in adrenocortical tumo...

Neuroendocrine tumors (NETs) and carcinomas (NECs) are a heterogeneous group of malignances whose incidence is increasing worldwide. First-line approach is represented by surgery, whereas an effective pharmacological treatment for disseminated and relapsing disease is still needed. Somatostatin (SS) receptors (SSTs) constitute the main suitable pharmacological targets for NETs therapy with SS analogs (SSAs). Nevertheless, a large proportion of NETs and most NECs, are unrespons...

Dopamine receptor type 2 (DRD2) agonists (DAs) are the first-choice treatment for PRL-secreting pituitary tumors due to their efficacy in reducing tumor size and hormonal secretion. However, DAs are poorly effective in non-functioning pituitary tumors (NFPTs), despite most of them express DRD2. No correlation between DAs clinical responsiveness and DRD2 expression was found, suggesting post-receptor alterations underlying resistance. DRD2 signaling pathways that control cell p...

The cAMP signaling pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). In adrenocortical cells cAMP induces dramatic changes in cell morphology accompanied by actin cytoskeleton rearrangements that precede steroidogenesis, the causal relationship between these events being still undefined. In this study we investigated cAMP effects on cytoskeleton rearrangements and steroidogenic response in mouse (Y1) and human adrenocortical tu...

Endocrine Connections 2013 2 196–207. DOI: 10.1530/EC-13-0049...

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor of the parafollicular thyroid C cells. Although somatostatin (SS) receptors (SSTs) are expressed by MTCs, treatment with octreotide, specific for SST2, has shown poor efficacy in reducing MTC proliferation, whereas pasireotide, a multi-receptor SS analogue with preferential binding to SST5, has recently demonstrated antiproliferative effects in persistent postoperative MTCs. In vitro data in human MTC ce...