Abstract
Abstract: :
Purpose: Recently, we identified a GAS3 family member, Epithelial Membrane Protein 2 (EMP2), in a screen for functional tumor suppressor genes. Specifically, we observed that reduced expression of EMP2 increased tumorigenicity in vivo, and profoundly decreased cell susceptibility to cytotoxic lymphocyte (CTL)-mediated killing in vitro. Biochemical studies indicated that EMP2 regulates the compartmentalization of critical membrane proteins between intracellular pools and the cellular membrane. Thus, we hypothesize that EMP2 plays a previously unappreciated role in trafficking of certain surface proteins. In this study we observed an interesting expression pattern for EMP2 in specific locations of the eye. Methods: Human and mouse eyes were used for expression studies by immunohistochemistry, Northern blot analysis, and RT-PCR. RNA was produced using the Qiagen RNeasy from dissected regions of the eye (retina, cornea, lens, optic nerve, ciliary body, iris, and sclera). An EMP2 cDNA probe, or EMP2-sprcific PCR primers were used for Northern Blot and RT-PCR analyses, respectively. A rabbit anti-mouse or anti-human EMP2 antibody was used for immunohistochemistry experiments. Results: When performing a Northern blot to determine the normal expression pattern of EMP2, we were surprised to find relatively high expression of this gene in the eye. Immunohistochemical analysis of the eye showed that EMP2 protein expression was restricted to the nerve fiber layer of the retina, the optic nerve, and the nonpigmented ciliary body epithelium. Northern blot and RT-PCR analyses of microdissected anatomic regions of the eye showed results consistent with those obtained by immunohistochemistry. Conclusions: The exact function of the newly described tumor suppressor gene, EMP2, is still a mystery. However, evidence from our laboratory suggests a role for EMP2 in protein trafficking. In this regard, the unique and specific tissue distribution of EMP2 in the eye is intriguing. Currently we are examining the function of this protein in these anatomic locations with regard to protein trafficking and maintenance of immune privilege. CR: none. Support: California Cancer Research Program (1NI0117).
Keywords: 417 gene/expression • 505 pathobiology • 610 tumors