Author/Authors :
Fedele، نويسنده , , Monica and Visone، نويسنده , , Rosa and De Martino، نويسنده , , Ivana and Troncone، نويسنده , , Giancarlo and Palmieri، نويسنده , , Dario and Battista، نويسنده , , Sabrina and Ciarmiello، نويسنده , , Andrea and Pallante، نويسنده , , Pierlorenzo and Arra، نويسنده , , Claudio and Melillo، نويسنده , , Rosa Marina and Helin، نويسنده , , Kristian and Croce، نويسنده , , Carlo Maria and Fusco، نويسنده , , Alfredo، نويسنده ,
Abstract :
Summary
gene amplification and overexpression in human prolactinomas and the development of pituitary adenomas in HMGA2 transgenic mice showed that HMGA2 plays a crucial role in pituitary tumorigenesis. We have explored the pRB/E2F1 pathway to investigate the mechanism by which HMGA2 acts. Here we show that HMGA2 interacts with pRB and induces E2F1 activity in mouse pituitary adenomas by displacing HDAC1 from the pRB/E2F1 complex—a process that results in E2F1 acetylation. We found that loss of E2F1 function (obtained by mating HMGA2 and E2F1−/− mice) suppressed pituitary tumorigenesis in HMGA2 mice. Thus, HMGA2-mediated E2F1 activation is a crucial event in the onset of these tumors in transgenic mice and probably also in human prolactinomas.
