肿瘤坏死因子α和幽门螺杆菌对胃癌中WNT10A的上调作用

Up-regulation of WNT10A by tumor necrosis factor alpha and Helicobacter pylori in gastric cancer.

作者信息

Kirikoshi H, Sekihara H, Katoh M

机构信息

Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.

出版信息

Int J Oncol. 2001 Sep;19(3):533-6.

PMID:11494032

Abstract

WNT signaling pathway is implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized WNT10A and WNT6, which are clustered in human chromosome 2q35 region. In this study, we investigated expression of WNT10A and WNT6 in gastric cancer. The 3.0- and 2.4-kb WNT10A mRNAs were expressed in gastric cancer cell lines MKN7, MKN45 and MKN74. The 2.0-kb WNT6 mRNA was expressed in gastric cancer cell lines MKN28 and MKN74. WNT10A was up-regulated in 3 out of 6 cases of primary gastric cancer, while WNT6 was not up-regulated in primary gastric cancer. Effects of inflammatory cytokines and Helicobacter pylori (H. pylori) on expression of WNT10A and WNT6 were next investigated. Interferon gamma (IFNgamma) failed to induce up-regulation of WNT10A and WNT6. Tumor necrosis factor alpha (TNFalpha) induced up-regulation of WNT10A in MKN45 cells. Up-regulation of WNT10A reached maximum at 6 h after TNFalpha treatment. H. pylori also induced up-regulation of WNT10A in MKN45 cells. These results strongly suggest that up-regulation of WNT10A induced by TNFalpha and H. pylori might play key roles in human gastric cancer through activation of WNT--beta-catenin--TCF signaling pathway.

摘要

WNT信号通路与癌症发生及胚胎发育有关。我们之前已克隆并鉴定了WNT10A和WNT6，它们聚集在人类染色体2q35区域。在本研究中，我们调查了WNT10A和WNT6在胃癌中的表达情况。3.0 kb和2.4 kb的WNT10A mRNA在胃癌细胞系MKN7、MKN45和MKN74中表达。2.0 kb的WNT6 mRNA在胃癌细胞系MKN28和MKN74中表达。在6例原发性胃癌中，有3例WNT10A上调，而原发性胃癌中WNT6未上调。接下来研究了炎性细胞因子和幽门螺杆菌（H. pylori）对WNT10A和WNT6表达的影响。γ干扰素（IFNγ）未能诱导WNT10A和WNT6上调。肿瘤坏死因子α（TNFα）诱导MKN45细胞中WNT10A上调。TNFα处理后6小时，WNT10A上调达到最大值。幽门螺杆菌也诱导MKN45细胞中WNT10A上调。这些结果强烈表明，TNFα和幽门螺杆菌诱导的WNT10A上调可能通过激活WNT-β-连环蛋白-TCF信号通路在人类胃癌中起关键作用。