Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.
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.
Fedele
Monica
M
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Federico II Università degli Studi di Napoli, via Pansini 5, 80131 Naples, Italy.
Battista
Sabrina
S
Kenyon
Lawrence
L
Baldassarre
Gustavo
G
Fidanza
Vincenzo
V
Klein-Szanto
Andres J P
AJ
Parlow
A F
AF
Visone
Rosa
R
Pierantoni
Giovanna M
GM
Outwater
Eric
E
Santoro
Massimo
M
Croce
Carlo M
CM
Fusco
Alfredo
A
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics; D005260:Female; D052776:Female Urogenital Diseases / Q000235:genetics; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000378:metabolism*; D025743:HMGA2 Protein / Q000235:genetics / Q000502:physiology*; D008297:Male; D052801:Male Urogenital Diseases; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics; D010641:Phenotype; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D014158:Transcription, Genetic; D019076:Transgenes
D025743:HMGA2 Protein; D011993:Recombinant Fusion Proteins; D011388:Prolactin; D013006:Growth Hormone