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Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas

Oncogene volume 21, pages 3190–3198 (2002)Cite this article

A Correction to this article was published on 09 December 2022

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Abstract

Overexpression of the HMGA2 gene is a common feature of neoplastic cells both in experimental and human models. Intragenic and extragenic HMGA2 rearrangements responsible for HMGA2 gene overexpression have been frequently detected in human benign tumours of mesenchymal origin. To better understand the role of HMGA2 overexpression in human tumorigenesis, we have generated transgenic mice carrying the HMGA2 gene under the transcriptional control of the cytomegalovirus promoter. High expression of the transgene was demonstrated in all the mouse tissues analysed, whereas no expression of the endogenous HMGA2 gene was detected in the same tissues from wild-type mice. In this study, two indipendent lines of transgenic mice have been generated. By 6 months of age, 85% of female animals of both transgenic lines developed pituitary adenomas secreting prolactin and growth hormone. The transgenic males developed the same phenotype with a lower penetrance (40%) and a longer latency period (about 18 months). Therefore, these data demonstrate that the overexpression of HMGA2 leads to the onset of mixed growth hormone/prolactin cell pituitary adenomas. These transgenic mice may represent an important tool for the study of this kind of neoplasia.

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Acknowledgements

We thank Andrea Vecchione for useful discussions about the autoptic analysis of mice, Chris Munnery for the technical expertise in performing the in situ double immunofluorescence staining and the Associazione Partenopea per le Ricerche Oncologiche (APRO) for its support. This work was supported by grants P01CA76259 and P30CA56036 from the National Cancer Institute to CM Croce and by grants from AIRC and MURST, projects ‘Terapie antineoplastiche innovative’ and ‘Piani di Potenziamento della Rete Scientifica e Tecnologica’. GM Pierantoni was supported by a fellowship from the FIRC.

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Authors and Affiliations

  1. Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli (Federico II), Naples, Italy

    Monica Fedele, Sabrina Battista, Rosa Visone, Giovanna M Pierantoni, Massimo Santoro & Alfredo Fusco

  2. Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA

    Monica Fedele, Sabrina Battista, Gustavo Baldassarre, Vincenzo Fidanza & Carlo M Croce

  3. Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA

    Lawrence Kenyon

  4. Experimental Histopathology, Fox-Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Andres J P Klein-Szanto

  5. National Hormone and Pituitary Program (NHPP), Harbour-UCLA Med Ctr, Torrance, California, USA

    A F Parlow

  6. Image Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA

    Eric Outwater

  7. Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università di Catanzaro, Catanzaro, Italy

    Alfredo Fusco

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  1. Monica Fedele
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  2. Sabrina Battista
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  3. Lawrence Kenyon
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  4. Gustavo Baldassarre
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  5. Vincenzo Fidanza
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  6. Andres J P Klein-Szanto
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  7. A F Parlow
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  8. Rosa Visone
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  9. Giovanna M Pierantoni
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  10. Eric Outwater
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  11. Massimo Santoro
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  12. Carlo M Croce
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  13. Alfredo Fusco
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Corresponding author

Correspondence to Alfredo Fusco.

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Fedele, M., Battista, S., Kenyon, L. et al. Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas. Oncogene 21, 3190–3198 (2002). https://doi.org/10.1038/sj.onc.1205428

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  • DOI: https://doi.org/10.1038/sj.onc.1205428

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