Up-regulation of WNT8B mRNA in human gastric cancer

Int J Oncol. 2002 Feb;20(2):343-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Exons
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Introns
  • Mutation / genetics
  • Polymerase Chain Reaction
  • Proteins / genetics*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Sequence Homology, Amino Acid
  • Stomach Neoplasms / genetics*
  • Tumor Cells, Cultured
  • Up-Regulation*
  • Wnt Proteins
  • Zebrafish Proteins*


  • DNA, Complementary
  • Proteins
  • RNA, Neoplasm
  • WNT8B protein, human
  • Wnt Proteins
  • Zebrafish Proteins