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Expression of a Novel Human Gene, Human Wings Apart-Like (hWAPL), Is Associated with Cervical Carcinogenesis and Tumor Progression

Departments of ¹ Pathology and ² Obstetrics–Gynecology, Tokyo Medical University, Shinjuku-ku, Tokyo; ³ Core Research for Evolutional Science and Technology Research Project, Japan Science and Technology Corp., Kawaguchi-shi, Saitama; ⁴ Shinanomachi Research Park, Keio University, Shinjuku-ku, Tokyo; ⁵ Division of Virology, National Cancer Center Research Institute, Chuo-ku, Tokyo; and ⁶ National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan

In Drosophila melanogaster, the wings apart-like (wapl) gene encodes a protein that regulates heterochromatin structure. Here, we characterize a novel human homologue of wapl (termed human WAPL; hWAPL). The hWAPL mRNA was predominantly expressed in uterine cervical cancer, with weak expression in all other normal and tumor tissues examined. hWAPL expression in benign epithelia was confined to the basal cell layers, whereas in dysplasias it increasingly appeared in more superficial cell layers and showed a significant correlation with severity of dysplasia. Diffuse hWAPL expression was found in all invasive squamous cell carcinomas examined. In addition, NIH3T3 cells overexpressing hWAPL developed into tumors on injection into nude mice. Furthermore, repression of hWAPL expression by RNA interference induced cell death in SiHa cells. These results demonstrate that hWAPL is associated with cell growth, and the hWAPL expression may play a significant role in cervical carcinogenesis and tumor progression.