ECE2014 Poster Presentations Pituitary Basic (<emphasis role="italic">Generously supported by IPSEN</emphasis>) (11 abstracts)
Functional characterization of a new deletion in CDKN1B 5′-UTR region
Mauro Di Ruvo 1 , Federico Tagliati 1 , Erica Gentilin 1 , Teresa Gagliano 1 , Natalia Pellegata 2 , Katiuscia Benfini 1 , Ettore degli Uberti 1 & Maria Chiara Zatelli 1
1University of Ferrara, Ferrara, Italy; 2Helmholtz Zentrum, Munich, Germany.
Introduction: CDKN1B gene, which encodes a cyclin-dependent kinase (Cdk) inhibitor, regulates the progression throughout G1 to S cell cycle progression. CDKN1B loss-of-function germinal mutations cause the multiple endocrine neoplasia type 4 syndrome (MEN4).
Objective: The aim of the study is the functional characterization of a new 4 bp deletion in CDKN1B 5′-UTR region, identified in an acromegalic patient.
Materials and methods: We assessed a functional in vitro study, based on firefly luciferase reporter gene, on the deleted promoter of human (MCF-7), murine (AtT20/D16V-F2) and rat (GH3) cell lines. Total mRNA and proteins were extracted from peripheral blood of the patient and control subjects to analyze CDKN1B/p27Kip1 expression. In addition, we evaluated p27Kip1 expression in tissue sections of the patient’s GH-secreting pituitary adenoma by immunohistochemistry.
Results: A novel heterozygous deletion in CDKN1B 5′-UTR region was identified in an acromegalic patient. The deletion extends from nucleotide −29 to −26 from the translation start site. Transcriptional activity of the deleted promoter is significantly decreased (~30–60% P<0.01). CDKN1B/p27Kip1 expression analysis of patient’s circulating leukocytes showed a significant reduction (~72%) in mRNA levels, while p27Kip1 protein levels are similar to WT controls. Immunohistochemistry shows a reduced p27Kip1 expression in the patient’s pituitary adenoma compared to the control.
Conclusions: Our data show that the identified deletion causes a significant reduction in promoter transcriptional activity and in CDKN1B mRNA expression, indicating a putative role of the deletion in the patient’s disease. Further studies are needed order to understand whether the deletion could impact protein function.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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