Kirikoshi Hiroyuki, Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Mol Med. 2002 Oct;10(4):507-11.
WNT signaling molecules, playing key roles in embryogenesis and carcinogenesis, are potent targets for regenerative medicine and clinical oncology. We have previously cloned and characterized the human orthologue of mouse proto-oncogene Wnt-10b using bioinformatics and cDNA-PCR. Human WNT10B is moderately expressed in MKN45 and MKN74 cells derived from human gastric cancer, and is up-regulated by tumor necrosis factor alpha (TNFalpha) in MKN45 cells. Here, expression and regulation of WNT10B in human cancer other than gastric cancer were investigated using cDNA-PCR. WNT10B mRNA was expressed in the majority of squamous cell carcinoma cell lines derived from esophageal cancer and cervical cancer. WNT10B mRNA was relatively highly expressed in TE3, TE6, TE10, TE11 (esophageal cancer), Hs700T (pancreatic cancer), SKG-IIIa, HeLa S3 (cervical cancer), and T-47D (breast cancer). Expression of WNT10B mRNA was up-regulated by beta-estradiol in MCF-7 cells expressing estrogen receptors. Expression of WNT10B mRNA was down-regulated by all-trans retinoic acid in NT2 cells with the potential of self renewal and neuronal differentiation. WNT10B might be implicated in self renewal of stem cells as well as in carcinogenesis through activation of the WNT - beta-catenin pathway.
WNT信号分子在胚胎发育和肿瘤发生过程中发挥关键作用，是再生医学和临床肿瘤学的有效靶点。我们之前利用生物信息学和cDNA-PCR克隆并鉴定了小鼠原癌基因Wnt-10b的人类同源基因。人类WNT10B在源自人类胃癌的MKN45和MKN74细胞中适度表达，并且在MKN45细胞中被肿瘤坏死因子α（TNFα）上调。在此，我们利用cDNA-PCR研究了WNT10B在胃癌以外的人类癌症中的表达及调控情况。WNT10B mRNA在大多数源自食管癌和宫颈癌的鳞状细胞癌细胞系中表达。WNT10B mRNA在TE3、TE6、TE10、TE11（食管癌）、Hs700T（胰腺癌）、SKG-IIIa、HeLa S3（宫颈癌）和T-47D（乳腺癌）中相对高表达。在表达雌激素受体的MCF-7细胞中，WNT10B mRNA的表达被β-雌二醇上调。在具有自我更新和神经元分化潜能的NT2细胞中，全反式维甲酸下调WNT10B mRNA的表达。WNT10B可能通过激活WNT-β-连环蛋白信号通路参与干细胞的自我更新以及肿瘤发生。
