Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Oncol. 2002 Feb;20(2):373-7.
We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15 by using bioinformatics, cDNA-library screening, cDNA-PCR, and RACE. WNT3 and WNT3A genes are two human paralogues of mouse proto-oncogene Wnt3, which induces carcinogenesis through activation of the beta-catenin - TCF signaling pathway. Here, regulation of WNT3 and WNT3A mRNAs in human cancer cell lines was investigated. WNT3 and WNT3A mRNAs were co-expressed in an embryonal carcinoma cell line NT2, which is reported to differentiate into postmitotic CNS neurons by treatment with retinoic acid for two weeks. Expression level of WNT3 mRNA in NT2 cells was not changed during 72 h after retinoic acid treatment, while expression of WNT3A mRNA was down-regulated in NT2 cells by retinoic acid. WNT3 and WNT3A mRNAs were also co-expressed in a breast cancer cell line MCF-7, and were down-regulated together by beta-estradiol in MCF-7 cells. Expression of WNT3 mRNA in a gastric cancer cell line MKN45 was not changed after treatment with tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFNgamma), and that of WNT3A mRNA was undetectable before and after treatment with TNFalpha or IFNgamma. WNT3A, down-regulated by retinoic acid in NT2 cells, might play key roles in the maintenance of NT2 cells in the undifferentiated proliferation stage through activation of the beta-catenin - TCF signaling pathway.
我们之前通过生物信息学、cDNA文库筛选、cDNA-PCR和RACE技术克隆并鉴定了人类WNT2B/WNT13、WNT3、WNT3A、WNT5B、WNT6、WNT7B、WNT8A、WNT10A、WNT10B、WNT11、WNT14以及WNT14B/WNT15。WNT3和WNT3A基因是小鼠原癌基因Wnt3的两个人类旁系同源基因，该基因通过激活β-连环蛋白-TCF信号通路诱导癌变。在此，我们研究了人类癌细胞系中WNT3和WNT3A mRNA的调控情况。WNT3和WNT3A mRNA在胚胎癌细胞系NT2中共表达，据报道，用视黄酸处理两周后，NT2可分化为有丝分裂后的中枢神经系统神经元。视黄酸处理后72小时内，NT2细胞中WNT3 mRNA的表达水平未发生变化，而视黄酸可使NT2细胞中WNT3A mRNA的表达下调。WNT3和WNT3A mRNA也在乳腺癌细胞系MCF-7中共表达，在MCF-7细胞中，β-雌二醇可使它们的表达共同下调。用肿瘤坏死因子α（TNFα）或干扰素γ（IFNγ）处理后，胃癌细胞系MKN45中WNT3 mRNA的表达未发生变化，用TNFα或IFNγ处理前后均未检测到WNT3A mRNA的表达。在NT2细胞中被视黄酸下调的WNT3A，可能通过激活β-连环蛋白-TCF信号通路，在维持NT2细胞处于未分化增殖阶段中发挥关键作用。
