Identification of Fetuin-B as a member of a cystatin-like gene family on mouse chromosome 16 with tumor suppressor activity

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.