E2F1 activation is responsible for pituitary adenomas induced by HMGA2 gene overexpression
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BioMed Central
Open Access
Review
E2F1 activation is responsible for pituitary adenomas induced by HMGA2 gene overexpression Monica Fedele1, Giovanna Maria Pierantoni1, Rosa Visone1 and Alfredo Fusco*1,2 Address: 1Istituto di Endocrinologia e Oncologia Sperimentale del CNR e Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli "Federico II", via S. Pansini, 5 80131 Napoli, Italy and 2NOGEC (Naples Oncogenomic Center) – CEINGE Biotecnologie Avanzate & SEMM – European School of Molecular Medicine – Naples Site, via Comunale Margherita 482, Naples, Italy Email: Monica Fedele - [email protected]; Giovanna Maria Pierantoni - [email protected]; Rosa Visone - [email protected]; Alfredo Fusco* - [email protected] * Corresponding author
Published: 17 August 2006 Cell Division 2006, 1:17
doi:10.1186/1747-1028-1-17
Received: 20 July 2006 Accepted: 17 August 2006
This article is available from: http://www.celldiv.com/content/1/1/17 © 2006 Fedele et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract The High Mobility Group protein HMGA2 is a nuclear architectural factor that plays a critical role in a wide range of biological processes including regulation of gene expression, embryogenesis and neoplastic transformation. Several studies are trying to identify the mechanisms by which HMGA2 protein is involved in each of these activities, and only recently some new significant insights are emerging from the study of transgenic and knock-out mice. Overexpression of HMGA2 gene leads to the onset of prolactin and GH-hormone induced pituitary adenomas in mice, suggesting a critical role of this protein in pituitary tumorigenesis. This was also confirmed in the human pathology by the finding that HMGA2 amplification and/or overexpression is present in human prolactinomas. This review focuses on recent data that explain the mechanism by which HMGA2 induces the development of pituitary adenomas in mice. This mechanism entails the activation of the E2F1 protein by the HMGA2-mediated displacement of HDAC1 from pRB protein.
Background Pituitary tumors constitute 10% of intracranial neoplasms, and are mostly benign with slow growth [1]. Most pituitary neoplasms secrete hormone gene products, leading to disturbed endocrine functions. Prolactinomas account for the most common type of pituitary adenomas [1,2], while about one-third of pituitary adenomas are not associated with clinical hypersecretory syndromes, but with symptoms of an intracranial mass that leads to headaches, hypopituitarism or visual-field disturbances, which are classified as non-functioning pituitary adenomas (NFPAs). The genesis of pituitary tumors is still mainly unknown, but the actual model supposes that genetic
alterations represent the initializing event that transfo
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