Frame S, Crombie R, Liddell J, Stuart D, Linardopoulos S, Nagase H, Portella G, Brown K, Street A, Akhurst R, Balmain A
CRC Beatson Laboratories, Department of Medical Oncology, Glasgow, UK.
Philos Trans R Soc Lond B Biol Sci. 1998 Jun 29;353(1370):839-45. doi: 10.1098/rstb.1998.0248.
Tumour formation relies on a complex combination of genetic and environmental factors. In particular, the contributions from inherited predisposition genes as well as carcinogens, for example from cigarettes or in the diet, are amongst the major contributors to tumorigenesis. Since the study of such processes in particularly difficult in human cancers, the availability of a well-defined model system is of obvious benefit. The mouse skin model of multistage carcinogenesis offers an excellent tool for the study of the target cells, the target genes and the biological events associated with neoplasia. In this system, tumorigenesis occurs in a series of defined stages, each of which is characterized by specific and reproducible alterations in genes such as H-ras, cyclin D1, p53 and p16INK4A. Additional changes occur in the production of, or response to, factors such as transforming growth factor beta (TGF beta). These genetic and biological alterations are mirrored in human tumours of epithelial origin. Hence, research into the general principles of tumour initiation, promotion and progression in the context of the mouse skin model is likely to prove valuable in the continual search for new methods for the diagnosis, prevention, and therapeutic treatment of human cancers.
肿瘤形成依赖于遗传和环境因素的复杂组合。特别是，遗传易感性基因以及致癌物（例如来自香烟或饮食中的致癌物）的作用是肿瘤发生的主要促成因素。由于在人类癌症中研究此类过程特别困难，因此拥有一个定义明确的模型系统显然是有益的。多阶段致癌作用的小鼠皮肤模型为研究靶细胞、靶基因以及与肿瘤形成相关的生物学事件提供了一个极好的工具。在这个系统中，肿瘤发生按一系列确定的阶段进行，每个阶段的特征是诸如H-ras、细胞周期蛋白D1、p53和p16INK4A等基因发生特定且可重复的改变。在诸如转化生长因子β（TGFβ）等因子的产生或对其的反应中也会发生其他变化。这些遗传和生物学改变在人类上皮源性肿瘤中也有体现。因此，在小鼠皮肤模型的背景下研究肿瘤起始、促进和进展的一般原则，可能会在不断寻找人类癌症诊断、预防和治疗新方法的过程中证明是有价值的。
