RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice
RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice
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DOI：
10.1038/onc.2010.428
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发表时间：
2011-01-01
期刊：
影响因子：
8
通讯作者：
Beermann, F.
中科院分区：
文献类型：
--
作者：
Schouwey, K.;Aydin, I. T.;Beermann, F.
Notch信号通路是一种普遍存在的细胞-细胞相互作用机制，在控制细胞增殖、细胞命运决定、分化或干细胞维持等过程中至关重要。最近的数据表明，Notch信号传导在黑素细胞中是RBP-J κ依赖性的，是负责哺乳动物皮肤和毛发着色的这些色素细胞存活所必需的。此外，Notch被认为在黑色素瘤中起致癌基因的作用，而在小鼠表皮中是肿瘤抑制因子。在这项研究中，我们解决了Notch信号在另一个群体的色素细胞形成的视网膜色素上皮（RPE）在哺乳动物眼睛的发展的影响。Notch在Tyrp 1：：NotchIC/degrees转基因小鼠中的组成性活性增强了RPE细胞增殖，并且所产生的RPE衍生的色素性肿瘤严重影响了整个眼睛结构。这种RPE细胞增殖依赖于转录因子RBP-J κ的存在，因为它在RPE中缺乏RBP-J κ的小鼠中被拯救。总之，RPE中的Notch信号传导使用依赖于转录因子RBP-J κ的经典途径。此外，它对于RPE发育是重要的，并且组成型Notch活性导致这些色素细胞的过度增殖和良性肿瘤。Oncogene（2011）30，313-322; doi：10.1038/onc.2010.428; 2010年9月20日在线发表
The Notch signaling pathway is an ubiquitous cell-cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-J kappa-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/degrees transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-J kappa, as it is rescued in mice lacking RBP-J kappa in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-J kappa. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells. Oncogene (2011) 30, 313-322; doi:10.1038/onc.2010.428; published online 20 September 2010