Mariaenrica Bellio

Early onset acromegaly associated with a novel deletion in CDKN1B 5′UTR region

Genetic alterations frequently are involved in the development of a pituitary adenoma in young age. We here characterize the functional role of a deletion in CDKN1B 5′-UTR region (c.-29_-26delAGAG) identified in an acromegalic patient that developed a growth hormone in pituitary adenoma during childhood. Our results show that the identified novel heterozygous deletion in the CDKN1B 5′-UTR region associates with a reduction in CDKN1B mRNA levels, a predicted altered secondary mRNA structure, and a reduced CDKN1B 5′-UTR transcriptional activity in vitro. The patient displayed loss of heterozygosity in the same CDKN1B 5′-UTR region at tissue level and the 5′UTR region containing the deleted sequence encompasses a GRE. These findings indicate that the identification of functional alterations of newly discovered genetic derangements need to be fully characterized and always correlated with the clinical manifestations.

PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line

PurposeInsulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion.MethodsCell viability, GH secretion, Akt, and Erk 1/2 phosphorylation levels in the rat GH3 cell line were assessed under treatment with IGF1 and/or everolimus, an mTOR inhitior.ResultsWe found that IGF1 improves rat GH3 somatotroph cell viability via the PI3K/Akt/mTOR pathway and confirmed that IGF1 exerts a negative feedback on GH secretion by a transcriptional mechanism. We demonstrated that the negative IGF1 loop on GH secretion requires Akt activation that seems to play a pivotal role in the control of GH secretion. Furthermore, Akt activation is independent of PI3K and probably mediated by mTORC2. In addition, we found that Erk 1/2 is not involved in GH3 cell viability regulation, but may have a role in controlling GH secretion, independently of IGF1.ConclusionOur data confirm that mTOR inhibitors may be useful to reduce pituitary adenoma cell viability, while Erk 1/2 pathway may be considered as a useful therapeutic target to control GH secretion. Our results open the field for further studies searching for effective drugs to control GH hyper-secretion.

VEGF autocrine secretion is enhanced by EGFR activation trough ERK1/2 phosphorylation in human adrenocortical carcinoma cell lines

ERK1/2 phosphorylation in human Adrenocortical Carcinoma cell lines Teresa Gagliano, Carmelina Di Pasquale, Erica Gentilin, Daniela Molè ,Martina Tassinari, Mariaenrica Bellio, Ettore degli Uberti, Maria Chiara Zatelli 1Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44121 Ferrara, Italy; 2Laboratorio in rete del Tecnopolo “Tecnologie delle terapie avanzate” (LTTA) of the University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy