Kirikoshi Hiroyuki, Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Int J Oncol. 2002 Jun;20(6):1183-7.
GIPC1/GIPC, GIPC2, and GIPC3 are a family of central PDZ-domain proteins. GIPC1/GIPC interacts with TGFbeta type III receptor, receptor tyrosine kinase TrkA, integrin alpha6A subunit, and GTPase-activating protein RGS-GAIP, while Xenopus homologue of human GIPCs interacts with Frizzled-3 (FZD3) class of WNT receptor. Here, we investigated expression of GIPC2 mRNA in human gastric, pancreatic, and breast cancer cell lines. GIPC2 mRNA was relatively highly expressed in OKAJIMA, TMK1, MKN45, and KATO-III cells derived from diffuse type of gastric cancer, but was almost undetectable in MKN7, MKN28, and MKN74 cells derived from intestinal type of gastric cancer as well as in other cell lines derived from pancreatic and breast cancer. Tumor necrosis factor alpha and interferon gamma, which are elevated in gastric mucosa with Helicobacter pylori infection, did not affect the expression level of GIPC2 mRNA in MKN45 cells. Up-regulation of GIPC2 mRNA was detected in 7 out of 10 cases of primary gastric cancer by using cDNA-PCR, and in 4 out of another 8 cases of primary gastric cancer by using expression array filter hybridization. GIPC2 might play important roles in human gastric cancer through modulation of growth factor signaling or cell adhesion.
GIPC1/GIPC、GIPC2和GIPC3是一类主要的含PDZ结构域的蛋白质。GIPC1/GIPC与转化生长因子βⅢ型受体、受体酪氨酸激酶TrkA、整合素α6A亚基以及GTP酶激活蛋白RGS - GAIP相互作用，而人类GIPCs的非洲爪蟾同源物与WNT受体的卷曲蛋白-3（FZD3）家族相互作用。在此，我们研究了GIPC2 mRNA在人胃癌、胰腺癌和乳腺癌细胞系中的表达情况。GIPC2 mRNA在源自弥漫型胃癌的冈岛、TMK1、MKN45和KATO - III细胞中相对高表达，但在源自肠型胃癌的MKN7、MKN28和MKN74细胞以及源自胰腺癌和乳腺癌的其他细胞系中几乎检测不到。在幽门螺杆菌感染的胃黏膜中升高的肿瘤坏死因子α和干扰素γ，并不影响MKN45细胞中GIPC2 mRNA的表达水平。通过使用cDNA - PCR，在10例原发性胃癌中有7例检测到GIPC2 mRNA上调，通过使用表达阵列滤膜杂交，在另外8例原发性胃癌中有4例检测到上调。GIPC2可能通过调节生长因子信号传导或细胞黏附在人类胃癌中发挥重要作用。
