Reduced membranous and ectopic cytoplasmic expression of beta -catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer

Int J Cancer. 2001 May 20;95(3):194-7. doi: 10.1002/1097-0215(20010520)95:3<194::aid-ijc1033>;2-m.


Beta-catenin is a component of the E-cadherin-catenin cell adhesion complex. It plays also a role in intracellular signaling and can function as an oncogene when it binds to the T-cell factor 4 (Tcf4)-binding site in the promoter region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of beta-catenin in relationship with cyclin D1 overexpression, tumor grade, clinicopathologic parameters and patients' survival in 43 ductal adenocarcinomas of the pancreas and 5 normal pancreatic tissues. We were able to show that, both reduced membranous beta-catenin expression (25 of 43, 58.1%) and accumulation of beta-catenin in the cytoplasm (28 of 43, 65.1%) correlated significantly with cyclin D1 overexpression (both p < 0.0005). Furthermore, we could show a clear correlation between reduced membranous expression and ectopic cytoplasmic expression of beta-catenin (p < 0.0005). Among patients with carcinomas showing no cytoplasmic expression, the 1-year survival was 86.6% whereas among patients with carcinomas showing cytoplasmic expression only 35.7% survived 1 year (p < 0.01). Co-precipitation experiments revealed reduced beta-catenin bound to the E-cadherin-catenin complex in pancreatic tumor tissues compared with normal pancreatic tissues. These results suggest that beta-catenin may be involved in the tumorigenesis of pancreatic cancer and exhibited its effects mainly by the transactivation of cyclin D1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Cell Membrane / metabolism
  • Cyclin D1 / metabolism*
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Precipitin Tests
  • Prognosis
  • Survival Analysis
  • Trans-Activators*
  • beta Catenin


  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Cyclin D1