Up-regulation of WNT8B mRNA in human gastric cancer.
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.
Saitoh
Tetsuroh
T
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Mine
Tetsuya
T
Katoh
Masaru
M
D000483:Alleles; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013274:Stomach Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D018076:DNA, Complementary; D011506:Proteins; D012334:RNA, Neoplasm; C490604:WNT8B protein, human; D051153:Wnt Proteins; D029961:Zebrafish Proteins