Alterations of frizzled (FzE3) and secreted frizzled related protein (hsFRP) expression in gastric cancer

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.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Cyclin D1 / analysis
  • Cyclin D1 / biosynthesis
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / biosynthesis
  • Down-Regulation
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Stomach Neoplasms / chemistry
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Trans-Activators*
  • Up-Regulation
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Neoplasm Proteins
  • Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Trans-Activators
  • beta Catenin
  • frizzled related protein-3
  • Cyclin D1