Kirikoshi Hiroyuki, Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Oncol. 2002 Apr;20(4):777-83.
Secreted-type glycoprotein WNTs bind to seven-transmembrane-type WNT receptors encoded by Frizzled genes (FZD1-FZD10) to transduce signals to the beta-catenin--TCF pathway, the JNK pathway, or the Ca(2+)-releasing pathway. Wrch1 gene is a down-stream target gene of Wnt1 in C57MG cells, and encodes a Cdc42-related GTPase with the potential to activate the JNK pathway. Here, we isolated human WRCH1 cDNAs (accession no. AB074878) from gastric cancer cell lines OKAJIMA, MKN7, MKN28, MKN45, MKN74, and KATO-III, all of which showed a nucleotide substitution (343 C-->T) without amino-acid substitution compared with WRCH1 cDNA isolated by another group. WRCH1 gene, consisting of at least 3 exons, was mapped to human chromosome 1q42.11-q42.3 by using bioinformatics. WRCH1 mRNA was more highly expressed in corpus callosum, hippocampus, cerebral cortex, and also in several parts within adult brain than in other normal tissues including stomach, pancreas, and placenta. Amounts of WRCH1 mRNA in 40 human cancer cell lines were lower than that in normal stomach, pancreas, or placenta. WRCH1 mRNA was significantly up-regulated in 4 cases of primary kidney tumors, 1 case each of primary colon, gastric, breast, ovarian, and uterus cancer. On the other hand, WRCH1 mRNA was significantly down-regulated in 6 cases of colon tumors, 2 cases of primary kidney cancer and breast cancer. Expression of WRCH1 mRNA was down-regulated by beta-estradiol in MCF-7 cells. This is the first report on comprehensive expression analyses on WRCH1 mRNA.
分泌型糖蛋白WNTs与由卷曲蛋白基因（FZD1 - FZD10）编码的七跨膜型WNT受体结合，从而将信号转导至β-连环蛋白-TCF途径、JNK途径或Ca(2+)释放途径。Wrch1基因是C57MG细胞中Wnt1的下游靶基因，编码一种与Cdc42相关的GTP酶，具有激活JNK途径的潜力。在此，我们从胃癌细胞系OKAJIMA、MKN7、MKN28、MKN45、MKN74和KATO-III中分离出人类WRCH1 cDNA（登录号AB074878），与另一组分离的WRCH1 cDNA相比，所有这些细胞系均显示出核苷酸替换（343 C→T）但无氨基酸替换。通过生物信息学方法，由至少3个外显子组成的WRCH1基因被定位到人类染色体1q42.11 - q42.3。WRCH1 mRNA在胼胝体、海马体、大脑皮层以及成人大脑的几个部位中的表达高于包括胃、胰腺和胎盘在内的其他正常组织。40个人类癌细胞系中WRCH1 mRNA的含量低于正常胃、胰腺或胎盘。在4例原发性肾肿瘤、1例原发性结肠癌、胃癌、乳腺癌、卵巢癌和子宫癌中，WRCH1 mRNA显著上调。另一方面，在6例结肠肿瘤、2例原发性肾癌和乳腺癌中，WRCH1 mRNA显著下调。在MCF-7细胞中，β-雌二醇可下调WRCH1 mRNA的表达。这是关于WRCH1 mRNA综合表达分析的首次报道。
