Protein Science and Engineering
We have recently reported that excess fibroblast growth factor-7 (FGF-7) in Krt12rtTA/rtTA/tetO-FGF-7 double transgenic mice induced by doxcycline (Dox) resulted in a corneal epithelial tumor resembling human ocular surface squamous neoplasia (OSSN) (Chikama et al. Am. J. Pathol. 172:638-649). Here, we further investigate the role of -catenin in mediating FGF-7 induced corneal tumorigenesis. Pannus surgically removed from OSSN patients all had nuclear - catenin and exhibited excess FGF-7. In vitro, FGF-7 induces stabilization and nuclear translocation of -catenin in human corneal epithelial cells. In vivo, conditional knock-out of -catenin gene (Ctnnb1) did not have significant effects on corneal morphogenesis or homeostasis, but abolished OSSN formation in Doxtreated Krt12rtTA/rtTA/tetO-FGF-7/tetO-Cre/Ctnnb1lox(E2-6)/lox(E2-6) mice. These results suggest that -catenin plays a pivotal role in mediating the formation of OSSN. Thus, the administration of inhibitor(s) that prevents activation of -catenin may be beneficial for treating OSSN.