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 over-expression 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3190-3198 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 21 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - May 9 2002 |
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Keywords
- Pit-1
- Pituitary adenomas
- Transgenic mice HMGA2
- Tumorigenesis
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas. / Fedele, Monica; Battista, Sabrina; Kenyon, Lawrence; Baldassarre, Gustavo; Fidanza, Vincenzo; Klein-Szanto, Andres J P; Parlow, A. F.; Visone, Rosa; Pierantoni, Giovanna M.; Outwater, Eric; Santoro, Massimo; Croce, Carlo M.; Fusco, Alfredo.
In: Oncogene, Vol. 21, No. 20, 09.05.2002, p. 3190-3198.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas
AU - Fedele, Monica
AU - Battista, Sabrina
AU - Kenyon, Lawrence
AU - Baldassarre, Gustavo
AU - Fidanza, Vincenzo
AU - Klein-Szanto, Andres J P
AU - Parlow, A. F.
AU - Visone, Rosa
AU - Pierantoni, Giovanna M.
AU - Outwater, Eric
AU - Santoro, Massimo
AU - Croce, Carlo M.
AU - Fusco, Alfredo
PY - 2002/5/9
Y1 - 2002/5/9
N2 - 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 over-expression 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.
AB - 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 over-expression 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.
KW - Pit-1
KW - Pituitary adenomas
KW - Transgenic mice HMGA2
KW - Tumorigenesis
UR - http://www.scopus.com/inward/record.url?scp=0037046499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037046499&partnerID=8YFLogxK
U2 - 10.1038/sj/onc/1205428
DO - 10.1038/sj/onc/1205428
M3 - Article
C2 - 12082634
VL - 21
SP - 3190
EP - 3198
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 20
ER -