Comparative genomics on Wnt8a and Wnt8b genes.

WNT family ligands transduce signals through FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, FZD10, LRP5, LRP6, ROR1, ROR2 and RYK. WNT1, WNT2, WNT2B, WNT3, WNT3A, WNT8A, WNT8B, WNT10A and WNT10B are canonical WNTs to activate WNT - beta-catenin pathway. Human WNT8A mRNA is expressed in NT2 cells with neuronal differentiation potential, while human WNT8B mRNA in diffuse type gastric cancer. Here, we identified and characterized the rat Wnt8a and Wnt8b genes by using bioinformatics. The rat Wnt8a gene, consisting of six exons, was located within AC134361.2 genome sequence. The rat Wnt8b gene, consisting of six exons, was located within AC105487.6 and AC103018.7 genome sequences. The rat Wnt8a (355 aa) and Wnt8b (350 aa) with 60.0% total-amino-acid identity were secreted-type proteins with 22 conserved Cys residues and two Asn-linked glycosylation sites. Wnt8b orthologs were more conserved than Wnt8a orthologs. GATA-binding site was located within conserved region of rat Wnt8b and human WNT8B promoters. GATA6 ESTs were expressed in diffuse type gastric cancer, and FGFR2 gene is reported preferentially amplified in diffuse type gastric cancer. KGF-FGFR2-PI3K-GATA6-WNT8B signaling cascade is predicted to play important roles in diffuse type gastric cancer. This is the first report on the rat Wnt8a and Wnt8b genes as well as on the conserved GATA-binding site within rat Wnt8b and human WNT8B promoters.