Jones Kevin B
Department of Orthopaedic Surgery and Center for Children's Cancer Research, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT 84112, USA.
Sarcoma. 2011;2011:694136. doi: 10.1155/2011/694136. Epub 2011 Feb 20.
Osteosarcoma remains a deadly malignancy afflicting adolescents and young adults. The lack of a precursor and the panoply of genetic aberrations present in identified osteosarcomas makes study of its initiation difficult. A number of candidate hypotheses have been tested in the mouse, a species with a higher background incidence of osteosarcoma. Chemical carcinogens, external beam radiation, and bone-seeking heavy metal radioisotopes have all proven to be osteosarcomagenic in wild-type mice. A number of oncogenes, introduced via integrating viruses or aberrantly activated from heritable genetic loci, participate in and can individually drive osteosarcomagenesis. Germline and conditional gene ablations in the form of some but not all aneuploidy-inducing genes, conventional tumor suppressors, and factors that function normally in mesenchymal differentiation have also proven osteosarcomagenic, especially in combinations that silence the Rb1 and p53 pathways. This paper reviews the rich history of mouse models of osteosarcomagenesis, what they have taught us about the human disease, and what future mouse experiments yet promise to teach.
骨肉瘤仍然是一种折磨青少年和年轻人的致命恶性肿瘤。由于缺乏前驱病变以及已确诊骨肉瘤中存在的大量基因畸变，对其起源的研究颇具难度。在骨肉瘤背景发病率较高的小鼠物种中，人们已经对一些候选假说进行了测试。化学致癌物、外照射放疗以及亲骨性重金属放射性同位素在野生型小鼠中均已被证明具有致骨肉瘤作用。通过整合病毒引入或从可遗传基因位点异常激活的一些癌基因参与并可单独驱动骨肉瘤发生。以某些（但并非全部）诱导非整倍体的基因、传统肿瘤抑制因子以及在间充质分化中正常发挥作用的因子形式存在的种系和条件性基因缺失也已被证明具有致骨肉瘤作用，尤其是在使Rb1和p53通路沉默的组合中。本文回顾了骨肉瘤发生小鼠模型的丰富历史、它们教给我们的有关人类疾病的知识以及未来小鼠实验有望教给我们的知识。
