Katoh M et al. (2001), WNT2B2 mRNA, up-regulated in primary gastric ca...

XB-ART-7980

Biochem Biophys Res Commun 2001 Dec 21;2895:1093-8. doi: 10.1006/bbrc.2001.6076.

Show Gene links Show Anatomy links

WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT- beta-catenin-TCF signaling pathway.

Katoh M , Kirikoshi H , Terasaki H , Shiokawa K .

???displayArticle.abstract???
Genetic alterations of WNT signaling molecules lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway. We have previously cloned and characterized WNT2B/WNT13 gene on human chromosome 1p13, which is homologous to proto-oncogene WNT2 on human chromosome 7q31. WNT2B1 and WNT2B2 mRNAs, generated from the WNT2B gene due to alternative splicing of the alternative promoter type, encode almost identical polypeptides with divergence in the N-terminal region. WNT2B2 mRNA rather than WNT2B1 mRNA is preferentially expressed in NT2 cells with the potential of neuronal differentiation. Here, we describe our investigations of expression of WNT2B mRNAs in various types of human primary cancer. Matched tumor/normal expression array analysis revealed that WNT2B mRNAs were significantly up-regulated in 2 of 8 cases of primary gastric cancer. WNT2B2 mRNA rather than WNT2B1 mRNA was found to be preferentially up-regulated in a case of primary gastric cancer (signet ring cell carcinoma). Function of WNT2B1 mRNA and that of WNT2B2 mRNA were investigated by using Xenopus axis duplication assay. Injection of synthetic WNT2B1 mRNA into the ventral marginal zone of fertilized Xenopus eggs at the 4-cell stage did not induce axis duplication. In contrast, ventral injection of synthetic WNT2B2 mRNA induced axis duplication in 90% of embryos (complete axis duplication, 24%). These results strongly suggest that WNT2B2 up-regulation in some cases of gastric cancer might lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway.

???displayArticle.pubmedLink??? 11741304
???displayArticle.link??? Biochem Biophys Res Commun

Species referenced: Xenopus laevis
Genes referenced: wnt2 wnt2b

???attribute.lit??? ???displayArticles.show???

	FIG. 1. Expression of WNT2B mRNAs in various types of human primary cancer. (A) Kidney tumors. (B) Gastric cancer. (C) Lung cancer. (D) Colon cancer. (E) Rectal cancer. (F) Prostate cancer. (G) Breast cancer. (H) Cervical cancer. (I) Uterus tumors. (J) Ovarian cancer. Matched tumor/normal expression array filter (Clontech Laboratories) was hybridized with [a-32P]dCTP-labeled WNT2B probe. WNT2B mRNAs were significantly up-regulated in 2 of 8 cases of primary gastric cancer.
	FIG. 2. Expression of WNT2B1 and WNT2B2 mRNAs in human gastric cancer. (A) Gastric cancer cell lines. Ten ng of poly(A)1 RNAs were used as templates for one-step cDNA-PCR. WNT2B1 cDNA (180 bp) was detected by 28 cycles of cDNA-PCR with PW2B1-01 and PW2B1-02 primers, WNT2B2 cDNA (181 bp) by 28 cycles of cDNAPCR with PW2B2-03 and PW2B2-04 primers, and b-actin cDNA (428 bp) by 17 cycles of cDNA-PCR with BACT2 and BACT3 primers. WNT2B1 mRNA was almost undetectable in 7 gastric cancer cell lines, while WNT2B2 mRNA was expressed in gastric cancer cell lines MKN1, MKN28, MKN45, and MKN74. (B) Primary gastric cancer. Fifteen ng of matched normal and tumor cDNAs from case 4 of primary gastric cancer with WNT2B up-regulation were used as templates for PCR. WNT2B1 cDNA was detected by 32 cycles of PCR with PW2B1-01 and PW2B1-02 primers, WNT2B2 cDNA by 32 cycles of PCR with PW2B2-03 and PW2B2-04 primers, and b-actin cDNA by 22 cycles of PCR with BACT2 and BACT3 primers. WNT2B2 mRNA rather than WNT2B1 mRNA was preferentially up-regulated in case 4 of primary gastric cancer (signet ring cell carcinoma).
	FIG. 3. Induction of Xenopus axis duplication by WNT2B2, not by WNT2B1. (A) Structure of WNT2B1 and WNT2B2. WNT2B1 and WNT2B2 are identical in the WNT-core domain (gray box), but divergent in the N-terminal region. N-terminal hydrophobic signal peptide (closed box) exist in WNT2B1, but not in WNT2B2. Amino acid numbers of WNT2B1 and WNT2B2 are also shown. (B) Xenopus axis duplication assay. Synthetic mRNA of b-globin (1 ng), WNT2B1 (1 ng), WNT2B2 (1 ng), or Xwnt-8 (0.5 pg) was injected into the ventral marginal zone of Xenopus embryos at the 4-cell stage. Ventral injection of WNT2B2 mRNA induced the secondary axis formation or axis duplication in Xenopus embryos. (C) Summary of Xenopus axis duplication assay. Complete axis duplication (additional head structure with eyes) is shown by closed bar, and partial axis duplication (additional head-like structure without eyes) by open bar. Ventral injection of WNT2B1 mRNA did not induce axis duplication. On the other hand, ventral injection of WNT2B2 mRNA induced complete axis duplication in 24% of embryos, and also partial axis duplication in 67% of embryos.