Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2

Mouse Frizzled-8, encoding a WNT receptor, is a potent cancer-associated gene to activate the beta-catenin-TCF pathway. However, these is a possibility that mouse Frizzled-8 might be a pseudogene, because structure and expression profile of mouse Frizzled-8 mRNA are still unclear. We have cloned and characterized the human Frizzled-8 (FZD8) gene, a human homologue of mouse Frizzled-8. Comparison between FZD8 genome clones and FZD8 cDNA clones isolated in this study revealed no intron within the FZD8 gene. FZD8 was found to encode a 694 amino-acid polypeptide with the frizzled-like cysteine-rich domain, seven transmembrane domains, and the C-terminal Ser/Thr-X-Val motif. Among human FZD family, FZD8 was most homologous to FZD5 (total amino-acid identity 69.1%). The 4.0-kb FZD8 mRNA was detected in fetal kidney and brain, and also in adult kidney, heart, pancreas, and skeletal muscle. These results indicate that human FZD8 is not a pseudogene. The FZD8 gene was mapped to human chromosome 10p11.2 by fluorescence in situ hybridization. Among human cancer cell lines, FZD8 was relatively highly expressed in HeLa S3 (cervical uterus cancer) and A549 (lung cancer). Up-regulation of FZD8 might play key roles in several types of human cancer through activation of the beta-catenin-TCF pathway.