WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT-β-catenin-TCF signaling pathway
WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT-β-catenin-TCF signaling pathway
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DOI：
10.1006/bbrc.2001.6076
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发表时间：
2001-12-21
影响因子：
3.1
通讯作者：
Shiokawa, K
中科院分区：
文献类型：
--
作者：
Katoh, M;Kirikoshi, H;Shiokawa, K
WNT 信号分子的遗传改变通过激活 β-catenin-TCF 信号通路导致癌变。我们之前克隆并鉴定了人类染色体1p13上的WNT2B/WNT13基因，该基因与人类染色体7q31上的原癌基因WNT2同源。由于替代启动子类型的选择性剪接而从 WNT2B 基因产生的 WNT2B1 和 WNT2B2 mRNA 编码几乎相同的多肽，但 N 端区域存在差异。 WNT2B2 mRNA而不是WNT2B1 mRNA优先在具有神经元分化潜力的NT2细胞中表达。在这里，我们描述了对 WNT2B mRNA 在各种类型的人类原发性癌症中表达的研究。匹配的肿瘤/正常表达阵列分析显示，8 例原发性胃癌中有 2 例 WNT2B mRNA 显着上调。研究发现，在原发性胃癌（印戒细胞癌）病例中，WNT2B2 mRNA 而非 WNT2B1 mRNA 优先上调。通过非洲爪蟾轴重复实验研究了 WNT2B1 mRNA 和 WNT2B2 mRNA 的功能。将合成的 WNT2B1 mRNA 注射到 4 细胞阶段的受精爪蟾卵的腹侧边缘区不会诱导轴复制。相比之下，腹腔注射合成 WNT2B2 mRNA 会诱导 90% 的胚胎出现轴复制（完全轴复制，24%）。这些结果强烈表明，在某些胃癌病例中，WNT2B2 上调可能通过激活 β-catenin-TCF 信号通路而导致癌变。 (C) 2001 年爱思唯尔科学。
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 protooncogene 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. (C) 2001 Elsevier Science.