To K F, Chan M W, Leung W K, Yu J, Tong J H, Lee T L, Chan F K, Sung J J
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales hospital, Shatin, NT, People's Republic of China.
Life Sci. 2001 Dec 14;70(4):483-9. doi: 10.1016/s0024-3205(01)01422-9.
Wnt signaling pathway is important for development and carcinogenesis. Alterations of this pathway, such as mutations in adenomatous polyposis coli (APC) gene and activation mutations of beta-catenin, would result in stabilization of beta-catenin and subsequent translocation to nucleus where genes are transcribed. Recently, a receptor of Wnt, FzE3 was found to be up-regulated in esophageal carcinoma while a non-receptor antagonist of Wnt, secreted frizzled related protein (hsFRP) was found to be down-regulated in some cancer. These findings suggested that FzE3 is a potential oncogene while hsFRP is a potential tumor suppressor gene. We aimed to investigate whether FzE3 and hsFRP were altered in gastric cancer. Twelve cases of gastric cancer, including 7 cases of intestinal type, 4 cases of diffuse type and I case of mixed type, were studied. FzE3 and hsFRP mRNAs were expressed in most of the paired normal gastric tissues. FzE3 was over-expressed in 9 cases (75%) of gastric carcinoma tissues while hsFRP was down-regulated in 2 cases (16%). Beta-catenin nuclear staining was identified in 3 cases (27%) and cyclin D1 was expressed in 5 cases (41%) of cancer samples. All these cases were associated with either up-regulation of FzE3 or down-regulation of hsFRP. Our results suggested that alterations of FzE3 or hsFRP were frequent in gastric cancer. These provide alternative mechanisms leading to activation of Wnt signaling pathway in gastric carcinogenesis.
Wnt信号通路对发育和致癌作用至关重要。该通路的改变，如腺瘤性息肉病大肠杆菌（APC）基因突变和β-连环蛋白的激活突变，会导致β-连环蛋白稳定，并随后转移至细胞核，在细胞核中进行基因转录。最近，发现Wnt的一种受体FzE3在食管癌中上调，而Wnt的一种非受体拮抗剂分泌型卷曲相关蛋白（hsFRP）在某些癌症中下调。这些发现表明FzE3是一种潜在的癌基因，而hsFRP是一种潜在的肿瘤抑制基因。我们旨在研究FzE3和hsFRP在胃癌中是否发生改变。研究了12例胃癌病例，包括7例肠型、4例弥漫型和1例混合型。FzE3和hsFRP mRNA在大多数配对的正常胃组织中表达。FzE3在9例（75%）胃癌组织中过度表达，而hsFRP在2例（16%）中下调。在3例（27%）癌症样本中发现β-连环蛋白核染色，5例（41%）中细胞周期蛋白D1表达。所有这些病例均与FzE3上调或hsFRP下调有关。我们的结果表明，FzE3或hsFRP的改变在胃癌中很常见。这些为胃癌发生过程中导致Wnt信号通路激活提供了替代机制。
