HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity
HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity
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DOI：
10.1016/j.ccr.2006.04.024
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发表时间：
2006-06-01
期刊：
影响因子：
50.3
通讯作者：
Fusco, Alfredo
中科院分区：
文献类型：
--
作者：
Fedele, Monica;Visone, Rosa;Fusco, Alfredo
HMGA2基因在人催乳素瘤中的扩增和过度表达以及HMGA2转基因小鼠中垂体腺瘤的发展表明HMGA2在垂体肿瘤发生中起着至关重要的作用。我们探索了 pRB/E2F1 通路来研究 HMGA2 的作用机制。在这里，我们发现 HMGA2 与 pRB 相互作用，并通过从 pRB/E2F1 复合物中取代 HDAC1 来诱导小鼠垂体腺瘤中的 E2F1 活性，这一过程会导致 E2F1 乙酰化。我们发现，E2F1 功能的丧失（通过 HMGA2 和 E2F1(-/-) 小鼠交配获得）抑制了 HMGA2 小鼠的垂体肿瘤发生。因此，HMGA2 介导的 E2F1 激活是转基因小鼠以及人类泌乳素瘤中这些肿瘤发生的关键事件。
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.