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

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 independent 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.

• Authors: Monica Fedele, Sabrina Battista, Lawrence Kenyon, Gustavo Baldassarre, Vincenzo Fidanza, Andres J P Klein-Szanto, A F Parlow, Rosa Visone, Giovanna M Pierantoni, Eric Outwater, Massimo Santoro, Carlo M Croce, Alfredo Fusco
• Journal: Oncogene (Oncogene) Vol. 21 Issue 20 Pg. 3190-8 (May 09 2002) ISSN: 0950-9232 [Print] England
• PMID: 12082634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HMGA2 Protein
• Recombinant Fusion Proteins
• Prolactin
• Growth Hormone

Topics

• Adenoma (genetics, metabolism)
• Animals
• Cell Transformation, Neoplastic (genetics)
• Congenital Abnormalities (genetics)
• Cytomegalovirus (genetics)
• Female
• Female Urogenital Diseases (genetics)
• Gene Expression Regulation
• Growth Hormone (metabolism)
• HMGA2 Protein (genetics, physiology)
• Male
• Male Urogenital Diseases
• Mice
• Mice, Transgenic
• Neoplasms, Experimental (genetics)
• Phenotype
• Pituitary Neoplasms (genetics, metabolism)
• Prolactin (metabolism)
• Prolactinoma (genetics, metabolism)
• Recombinant Fusion Proteins (biosynthesis, physiology)
• Transcription, Genetic
• Transgenes