Title : Up-regulation of
WNT8B mRNA in human gastric cancer
Abstract :
- WNT - beta-catenin - TCF signaling pathway is activated by Xenopus wnt-8 ( Xwnt-8 ) during Xenopus early development, and dysregulated activation of beta-catenin - TCF signaling pathway in mammalian cells leads to carcinogenesis
- We have previously cloned and characterized human WNT8A , one of human orthologues of Xwnt-8
- Here, we cloned and characterized human WNT8B by using bioinformatics, cDNA-PCR, and RACE
- WNT8B gene of about 23-kb in size consisted of six exons, and encoded a 351-amino-acid polypeptide with the N-terminal signal peptide and two N-linked glycosylation sites
- C-terminal region of WNT8B , WNT8A , WNT2 , and WNT2B were longer than that of other human WNTs
- Thirty-five nucleotide changes between WNT8B isolated by us and WNT8B isolated by another group resulted in Gly230Ala and Arg284Leu amino-acid substitutions
- Gly230 and Arg284 of WNT8B were conserved in WNT8A
- Gly230-Arg284 WNT8B allele was also identified in human genome draft sequences AL133352.10, AL359759.18, and human EST BF732616
- These results indicate that the Gly230-Arg284 WNT8B cDNA isolated in this study is derived from the more common WNT8B allele
- WNT8B mRNAs of 4.4- and 3.5-kb in size were weakly detected in a colorectal cancer cell line SW480, but were undetectable in any normal human tissues by using Northern blot analyses
- WNT8B was significantly up-regulated in gastric cancer cell lines KATO-III (signet-ring cell carcinoma) and MKN45 (poorly differentiated adenocarcinoma), and also in 5 out of 10 cases of primary gastric cancer
- WNT8B might play key roles in gastric cancer through activation of the beta-catenin - TCF signaling pathway