HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity

被引：232

作者：

Fedele, Monica

Visone, Rosa

De Martino, Ivana

Troncone, Giancarlo

Palmieri, Dario

Battista, Sabrina

Ciarmiello, Andrea

Pallante, Pierlorenzo

Arra, Claudio

Melillo, Rosa Marina

Helin, Kristian

Croce, Carlo Maria

Fusco, Alfredo ^{[1
]}

机构：

[1] Univ Naples Federico II, CNR, Ist Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy

[2] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy

[3] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA

[4] Univ Naples Federico II, Dipartimento Anat Patol, I-80131 Naples, Italy

[5] Ist Tumori Napoli, Fdn G Pascale, I-80131 Naples, Italy

[6] Biotech Res & Innovat Ctr, DK-2100 Copenhagen, Denmark

[7] European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy

[8] CEINGE, NOGEC, Naples Oncogenom Ctr, Naples, Italy

来源：

CANCER CELL | 2006年 / 9卷 / 06期

关键词：

D O I：

10.1016/j.ccr.2006.04.024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：459 / 471

页数：13

共 27 条

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