Hsu Ssucheng J, Nagase Hiroki, Balmain Allan
University of California at San Francisco Comprehensive Cancer Center, Box 0875, San Francisco, CA 94143-0875, USA.
Genome. 2004 Oct;47(5):931-46. doi: 10.1139/g04-043.
Studies of mouse models for multistage carcinogenesis have led to the identification of a susceptibility locus for skin tumor development (Skts9) in the proximal region of mouse chromosome 16. This chromosome region shows a loss of heterozygosity or an allelic imbalance in mouse skin and pancreatic islet carcinoma, and has been associated with angiogenesis. The microsatellite marker D16Mit2, which has the strongest linkage to skin tumor susceptibility, was used to screen a bacterial artificial chromosome (BAC) library, leading to the identification of the histidine-rich glycoprotein (Hrg) and Fetuin-B as the most tightly linked genes. These genes are members of a cystatin-like superfamily that includes the neighboring genes Kng and Ahsg/Fetuin. Overexpression of Fetuin-B in skin squamous carcinoma cells led to suppression of tumor growth in nude mice. The neighboring genes Kng and Ahsg also have potential roles in angiogenesis and (or) tumor development, and several genes in this locus may be candidates for the Skts9 gene.
对多阶段致癌作用小鼠模型的研究已导致在小鼠16号染色体近端区域鉴定出一个皮肤肿瘤发生的易感位点（Skts9）。该染色体区域在小鼠皮肤和胰岛癌中显示杂合性缺失或等位基因失衡，并且与血管生成有关。与皮肤肿瘤易感性具有最强连锁关系的微卫星标记D16Mit2被用于筛选细菌人工染色体（BAC）文库，从而鉴定出富含组氨酸的糖蛋白（Hrg）和胎球蛋白-B为最紧密连锁的基因。这些基因是一个胱抑素样超家族的成员，该超家族包括相邻基因Kng和Ahsg/胎球蛋白。胎球蛋白-B在皮肤鳞状癌细胞中的过表达导致裸鼠肿瘤生长受到抑制。相邻基因Kng和Ahsg在血管生成和（或）肿瘤发生中也具有潜在作用，并且该位点的几个基因可能是Skts9基因的候选基因。
