唐氏綜合癥由21號(hào)染色體一個(gè)額外版本的存在（一種被稱為“三體性”的狀態(tài)）引起，而且人們知道某些腫瘤的生長(zhǎng)在這種遺傳病中被抑制,。
用一個(gè)唐氏綜合癥小鼠模型所做的一項(xiàng)研究指出了一個(gè)抗腫瘤機(jī)制：通過(guò)四個(gè)基因的過(guò)度 表達(dá)來(lái)抑制腫瘤血管生成,，這四個(gè)基因分別是兩個(gè)假設(shè)的抗血管生成基因（ADAMTS1 和 ERG10）及兩個(gè)以前沒(méi)有與血管生成聯(lián)系在一起的新的內(nèi)皮細(xì)胞特定基因（JAM-B12和 PTTG1IP）。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature09106
Tumour angiogenesis is reduced in the Tc1 mouse model of Down’s syndrome
Louise E. Reynolds1, Alan R. Watson1,14, Marianne Baker1,14, Tania A. Jones3, Gabriela D’Amico1, Stephen D. Robinson1, Carine Joffre2, Sarah Garrido-Urbani5, Juan Carlos Rodriguez-Manzaneque6, Estefanía Martino-Echarri6, Michel Aurrand-Lions7, Denise Sheer3, Franca Dagna-Bricarelli8, Dean Nizetic4, Christopher J. McCabe9, Andrew S. Turnell10, Stephanie Kermorgant2, Beat A. Imhof5, Ralf Adams11, Elizabeth M. C. Fisher12, Victor L. J. Tybulewicz13, Ian R. Hart2 & Kairbaan M. Hodivala-Dilke1
Down’s syndrome (DS) is a genetic disorder caused by full or partial trisomy of human chromosome 21 and presents with many clinical phenotypes including a reduced incidence of solid tumours1, 2. Recent work with the Ts65Dn model of DS, which has orthologues of about 50% of the genes on chromosome 21 (Hsa21), has indicated that three copies of the ETS2 (ref. 3) or DS candidate region 1 (DSCR1) genes4 (a previously known suppressor of angiogenesis5, 6) is sufficient to inhibit tumour growth. Here we use the Tc1 transchromosomic mouse model of DS7 to dissect the contribution of extra copies of genes on Hsa21 to tumour angiogenesis. This mouse expresses roughly 81% of Hsa21 genes but not the human DSCR1 region. We transplanted B16F0 and Lewis lung carcinoma tumour cells into Tc1 mice and showed that growth of these tumours was substantially reduced compared with wild-type littermate controls. Furthermore, tumour angiogenesis was significantly repressed in Tc1 mice. In particular, in vitro and in vivo angiogenic responses to vascular endothelial growth factor (VEGF) were inhibited. Examination of the genes on the segment of Hsa21 in Tc1 mice identified putative anti-angiogenic genes (ADAMTS18, 9and ERG10) and novel endothelial cell-specific genes11, never previously shown to be involved in angiogenesis (JAM-B12 and PTTG1IP), that, when overexpressed, are responsible for inhibiting angiogenic responses to VEGF. Three copies of these genes within the stromal compartment reduced tumour angiogenesis, explaining the reduced tumour growth in DS. Furthermore, we expect that, in addition to the candidate genes that we show to be involved in the repression of angiogenesis, the Tc1 mouse model of DS will permit the identification of other endothelium-specific anti-angiogenic targets relevant to a broad spectrum of cancer patients.
Adhesion and Angiogenesis Laboratory, Barts Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK
Centre for Tumour Biology, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK
Neuroscience Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Institute of Cell and Molecular Sciences, 4 Newark Street, London E1 2AD, UK
Paediatrics Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Institute of Cell and Molecular Sciences, 4 Newark Street, London E1 2AD, UK
Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School (CMU), rue Michel Servet 1, CH-1211 Geneva, Switzerland
GENYO, Avenida Del Conocimiento, s/n Armilla 18100, Granada, Spain
INSERM, 27, Boulevard Lei Roure, 13009 Marseille, France
Human Genetics Institute, Galliere Hospital, Via Volta 10, 16128 Genoa, Italy
School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK
School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK
Max Planck Institute for Molecular Biomedicine, R?ntgenstrasse 20, D-48149 Münster, Germany
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
