Saitoh T, Katoh M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Int J Oncol. 2001 Aug;19(2):311-5. doi: 10.3892/ijo.19.2.311.
FRAT1 and FRAT2 are cancer-associated genes encoding GSK-3beta-binding proteins. Over-expression of FRAT1 or FRAT2 lead to carcinogenesis through activation of WNT--beta-catenin--TCF signaling pathway. We have previously cloned and characterized FRAT2. Here, we found that FRAT1 and FRAT2 genes were clustered in the human chromosome 10q24.1 region. Blast search revealed that FRAT1 and FRAT2 genes, consisting of a single exon, were located together on human genome draft sequences AC006098.1 and AL355490.7, corresponding to the human chromosome 10q24.1 region. FRAT1 and FRAT2 genes were clustered in a tail to tail manner with an interval of about 10.7 kb. The 2.7-kb FRAT1 mRNA was relatively highly expressed in fetal brain, adult spleen, pancreas, HeLa S3 (cervical cancer), and K-562 (chronic myelogenous leukemia). FRAT1 and FRAT2 were co-expressed in 7 gastric cancer cell lines and 10 cases of primary gastric cancer, and were up-regulated together in gastric cancer cell line TMK1 and 2 cases of primary gastric cancer. These results indicated that FRAT1 and FRAT2 genes were up-regulated together in several cases of human gastric cancer. Up-regulation of FRAT1 and FRAT2 in gastric cancer might lead to carcinogenesis through activation of WNT--beta-catenin--TCF signaling pathway.
FRAT1和FRAT2是与癌症相关的基因，编码与糖原合成酶激酶-3β（GSK-3β）结合的蛋白。FRAT1或FRAT2的过表达通过激活WNT-β-连环蛋白-TCF信号通路导致肿瘤发生。我们之前已经克隆并鉴定了FRAT2。在此，我们发现FRAT1和FRAT2基因聚集在人类染色体10q24.1区域。Blast搜索显示，由单个外显子组成的FRAT1和FRAT2基因共同位于人类基因组草图序列AC006098.1和AL355490.7上，对应于人类染色体10q24.1区域。FRAT1和FRAT2基因以尾对尾的方式聚集，间隔约10.7 kb。2.7 kb的FRAT1 mRNA在胎儿脑、成人脾脏、胰腺、HeLa S3（宫颈癌）和K-562（慢性粒细胞白血病）中相对高表达。FRAT1和FRAT2在7种胃癌细胞系和10例原发性胃癌中共同表达，并在胃癌细胞系TMK1和2例原发性胃癌中共同上调。这些结果表明，FRAT1和FRAT2基因在几例人类胃癌中共同上调。FRAT1和FRAT2在胃癌中的上调可能通过激活WNT-β-连环蛋白-TCF信号通路导致肿瘤发生。
