Nature：癌症也有“道义”

　　

生物通报道，近日Nature一篇文章报道唐氏综合症患者体内有一个基因会减缓肿瘤的生长速度，抑制癌细胞蔓延，文章Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1发表在Nature在线版上。

 

也许就像人们常说的，上帝是公平的，他为你关闭了一扇门时，会为你打开一扇窗。癌症也是讲道义的，命运的厄运不会一再的降临到苦难人的身上。

 

唐氏综合症（21-三体综合症）又名“先天愚型”，包含一系列的遗传病，其中最具代表性的第21对染色体的三体现象，会导致包括学习障碍、智能障碍和残疾等高度畸形。

 

据报道，唐氏综合症患者患各种癌症的几率比常人低，人们猜测这可能与其21号染色体上多出的一条染色体上的某些基因表达的有关。据介绍，1区的DSCR1（也称RCAN1）基因被认为是降低癌症发生率的可能基因，它编码的蛋白能抑制血管内皮生长因子（VEGF）介导的血管发生信号传导。

 

在本研究中，Zygmunt Galdzicki和Sandra Ryeom等人发现，唐氏综合症患者和唐氏综合症小鼠模型体内的组织中DSCR1的表达量比正常的高。研究人员尝试在提高DSCR1在癌症模型小鼠体内的表达量，结果发现能有效的抑制肿瘤血管生长，进而抑制肿瘤发生。

 

这些研究结果证实，唐氏综合症患者引起特殊的染色体而降低了癌症的发生率。并且，表明DSCR1是通过神经钙蛋白信号调节肿瘤血管生长的基因。DSCR1可能成为癌症治疗的新靶位。

（生物通 小茜）

生物通推荐原文检索：Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1

Kwan-Hyuck Baek1,8, Alexander Zaslavsky1,8, Ryan C. Lynch1,8, Carmella Britt1, Yoshiaki Okada2, Richard J. Siarey3, M. William Lensch4, In-Hyun Park4, Sam S. Yoon5, Takashi Minami6, Julie R. Korenberg7, Judah Folkman1, George Q. Daley4, William C. Aird2, Zygmunt Galdzicki3 & Sandra Ryeom1

 

Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Massachusetts 02115, USA

Center for Vascular Biology Research, Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA

Department of Anatomy, Physiology and Genetic, Neuroscience, Molecular and Cellular Biology Program, School of Medicine, Uniformed Services University of the Health Services, Bethesda, Maryland 20814, USA

Department of Medicine, Division of Pediatric Hematology Oncology, Children's Hospital Boston, and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA

Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, Maryland 02114, USA

Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, 153-8904, Japan

Department of Pediatrics and The Brain Institute, The University of Utah, Salt Lake City, Utah 84108, USA

These authors contributed equally to this work.

【Abstract】

The incidence of many cancer types is significantly reduced in individuals with Down's syndrome1, 2, 3, 4, and it is thought that this broad cancer protection is conferred by the increased expression of one or more of the 231 supernumerary genes on the extra copy of chromosome 21. One such gene is Down's syndrome candidate region-1 (DSCR1, also known as RCAN1), which encodes a protein that suppresses vascular endothelial growth factor (VEGF)-mediated angiogenic signalling by the calcineurin pathway5, 6, 7, 8, 9, 10. Here we show that DSCR1 is increased in Down's syndrome tissues and in a mouse model of Down's syndrome. Furthermore, we show that the modest increase in expression afforded by a single extra transgenic copy of Dscr1 is sufficient to confer significant suppression of tumour growth in mice, and that such resistance is a consequence of a deficit in tumour angiogenesis arising from suppression of the calcineurin pathway. We also provide evidence that attenuation of calcineurin activity by DSCR1, together with another chromosome 21 gene Dyrk1a, may be sufficient to markedly diminish angiogenesis. These data provide a mechanism for the reduced cancer incidence in Down's syndrome and identify the calcineurin signalling pathway, and its regulators DSCR1 and DYRK1A, as potential therapeutic targets in cancers arising in all individuals.