HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity

Monica Fedele, Rosa Visone, Ivana De Martino, Giancarlo Troncone, Dario Palmieri, Sabrina Battista, Andrea Ciarmiello, Pierlorenzo Pallante, Claudio Arra, Rosa Marina Melillo, Kristian Helin, Carlo Maria Croce, Alfredo Fusco

Research output: Contribution to journalArticle

Abstract

HMGA2 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.

Original languageEnglish
Pages (from-to)459-471
Number of pages13
JournalCancer Cell
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 13 2006

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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  • Cite this

    Fedele, M., Visone, R., De Martino, I., Troncone, G., Palmieri, D., Battista, S., Ciarmiello, A., Pallante, P., Arra, C., Melillo, R. M., Helin, K., Croce, C. M., & Fusco, A. (2006). HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity. Cancer Cell, 9(6), 459-471. https://doi.org/10.1016/j.ccr.2006.04.024