Kirikoshi H, Sekihara H, Katoh M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Oncol. 2001 Dec;19(6):1221-5. doi: 10.3892/ijo.19.6.1221.
WNT proteins play key roles in carcinogenesis. We have previously cloned and characterized WNT14 and WNT14B/WNT15. WNT14 and WNT3A genes are clustered on human chromosome 1q42, while WNT14B and WNT3 genes are clustered on human chromosome 17q21. Here, we investigated expression of WNT14 and WNT14B mRNAs in human cancer. WNT14 was significantly up-regulated in 1 out of 9 cases of primary breast cancer. WNT14B was not expressed in primary breast, gastric and colorectal cancers. Among 3 human breast cancer cell lines, WNT14 mRNA was expressed in T-47D cells, and weakly expressed in MCF-7 cells. WNT14 mRNA was also detected in 7 out of 7 pancreatic cancer cell lines, 12 out of 12 esophageal cancer cell lines, 4 out of 4 cervical cancer cell lines, and 5 out of 7 brain tumor cell lines by using cDNA-PCR. These results indicate that WNT14 rather than WNT14B is preferentially expressed in various types of human cancer, such as breast cancer, gastric cancer, and pancreatic cancer. WNT14 mRNA was up-regulated by interferon gamma (IFNgamma), but not by tumor necrosis factor alpha (TNFalpha), in MKN45 cells derived from gastric cancer, while expression of WNT14B mRNA was not affected by IFNgamma and TNFalpha in MKN45 cells. Although expression of WNT14 mRNA was not affected by beta-estradiol in MCF-7 cells, WNT14B mRNA was transiently up-regulated by beta-estradiol in MCF-7 cells. These results indicate that WNT14 is a target gene of IFNgamma in MKN45 cells, and that WNT14B is a target gene of estrogen in MCF-7 cells.
WNT蛋白在肿瘤发生过程中发挥关键作用。我们之前已克隆并鉴定了WNT14和WNT14B/WNT15。WNT14和WNT3A基因簇集在人类染色体1q42上，而WNT14B和WNT3基因簇集在人类染色体17q21上。在此，我们研究了WNT14和WNT14B mRNA在人类癌症中的表达情况。在9例原发性乳腺癌中有1例WNT14显著上调。原发性乳腺癌、胃癌和结直肠癌中未检测到WNT14B的表达。在3种人类乳腺癌细胞系中，WNT14 mRNA在T-47D细胞中表达，在MCF-7细胞中弱表达。通过cDNA-PCR检测，在7种胰腺癌细胞系中的7种、12种食管癌细胞系中的12种、4种宫颈癌细胞系中的4种以及7种脑肿瘤细胞系中的5种中也检测到了WNT14 mRNA。这些结果表明，在乳腺癌、胃癌和胰腺癌等多种人类癌症中，WNT14而非WNT14B优先表达。在源自胃癌的MKN45细胞中，WNT14 mRNA受干扰素γ（IFNγ）上调，但不受肿瘤坏死因子α（TNFα）影响，而MKN45细胞中WNT14B mRNA的表达不受IFNγ和TNFα影响。虽然MCF-7细胞中WNT14 mRNA的表达不受β-雌二醇影响，但MCF-7细胞中WNT14B mRNA受β-雌二醇短暂上调。这些结果表明，WNT14是MKN45细胞中IFNγ的靶基因，而WNT14B是MCF-7细胞中雌激素的靶基因。
