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  • Original Paper
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Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas

Abstract

Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/prolactin cell pituitary adenomas and natural killer (NK)-T/NK cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.

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Acknowledgements

We are grateful to Andrea Affuso for his helpful advices about mice management, Antonio Luciano for the animal care and Dario Palmieri for the technical assistance. We thank Fabrizio Pane for the DERL-7 cell line and the Associazione Partenopea per le Ricerche Oncologiche (APRO) for its support. This work was also supported by grants from AIRC and MURST, projects ‘Terapie antineoplastiche innovative’ and ‘Piani di Potenziamento della Rete Scientifica e Tecnologica’. We are grateful to Jean Ann Gilder for editing the text.

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Correspondence to Alfredo Fusco.

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Fedele, M., Pentimalli, F., Baldassarre, G. et al. Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas. Oncogene 24, 3427–3435 (2005). https://doi.org/10.1038/sj.onc.1208501

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