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¹ Dipartimento di Biologia e Patologia Cellulare e Molecolare and Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, University of Naples ‘Federico II’, via Pansini 5, 80131 Naples, Italy
² Dipartimento di Scienze Neurologiche, Divisione di Neurochirurgia, University of Naples ‘Federico II’, Naples, Italy
³ Dipartimento di Medicina Sperimentale, II University of Naples, Naples, Italy
⁴ Istituto dei Tumori di Napoli Fondazione ‘G Pascale’, Naples, Italy
⁵ Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
⁶ Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, University of Naples ‘Federico II’, Naples, Italy
⁷ NOGEC (Naples Oncogenomic Center), CEINGE Biotecnologie Avanzate and SEMM, European School of Molecular Medicine, Naples, Italy

(Correspondence should be addressed to A Fusco; Email: afusco{at}napoli.com)

The high-mobility group A (HMGA) family of proteins orchestrates the assembly of nucleoprotein structures playing important roles in gene transcription, recombination, and chromatin structure through a complex network of protein–DNA and protein–protein interactions. Recently, we have generated transgenic mice carrying wild type or truncated HMGA2 genes under the transcriptional control of the cytomegalovirus promoter. These mice developed pituitary adenomas secreting prolactin and GH mainly due to an increased E2F1 activity, directly consequent to the HMGA2 overexpression. To identify other genes involved in the process of pituitary tumorigenesis induced by the HMGA2 gene, in this study we have analyzed the gene expression profile of three HMGA2-pituitary adenomas in comparison with a pool of ten normal pituitary glands from control mice, using the Affymetrix MG MU11K oligonucleotide array representing ~13 000 unique genes. We have identified 82 transcripts that increased and 72 transcripts that decreased at least four-fold in all the mice pituitary adenomas analyzed compared with normal pituitary glands. Among these genes, we focused our attention on the Mia/Cd-rap gene, whose expression was essentially suppressed in all of the pituitary adenomas tested by the microarray. We demonstrated that the HMGA proteins directly bind to the promoter of the Mia/Cd-rap gene and are able to downregulate its expression. In order to understand a possible role of Mia/Cd-rap in pituitary cell growth, we performed a colony assay in GH3 and GH4 cells. Interestingly, Mia/Cd-rap expression inhibits their proliferation, suggesting a potential tumor suppressor role of Mia/Cd-rap in pituitary cells.

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				I. De Martino, R. Visone, A. Wierinckx, D. Palmieri, A. Ferraro, P. Cappabianca, G. Chiappetta, F. Forzati, G. Lombardi, A. Colao, et al. HMGA Proteins Up-regulate CCNB2 Gene in Mouse and Human Pituitary Adenomas Cancer Res., March 1, 2009; 69(5): 1844 - 1850. [Abstract] [Full Text] [PDF]