Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression

Oncology. 2007;73(1-2):112-7. doi: 10.1159/000120999. Epub 2008 Mar 13.


Objective: The Wnt/beta-catenin signaling cascade is an important signal transduction pathway in human cancers. Overexpression of beta-catenin and its downstream effector, cyclin D1, is implicated in malignant transformation and acquisition of an invasive tumor phenotype. This study aimed to determine the clinical significance of Wnt/beta-catenin canonical pathway components in breast cancer.

Methods: Expression of beta-catenin, dishevelled (Dvl) and cyclin D1 was examined in invasive ductal carcinomas (IDCs) of the breast by immunohistochemical analysis.

Results: Of the 98 IDCs analyzed, 30% of tumors displayed both nuclear and cytoplasmic staining of Dvl protein, while 52% showed nuclear localization. Loss of cell surface beta-catenin was observed in 66% of breast carcinomas, whereas nuclear expression was observed in 48% IDCs. Cyclin D1 overexpression was observed in 60% IDCs; 31/59 (53%) of these tumors showed nuclear expression of beta-catenin, suggesting upregulation of the canonical Wnt/beta-catenin pathway. Our study demonstrates a significant association between nuclear localization of Dvl and beta-catenin (p < 0.01, OR = 15.8).

Conclusion: To our knowledge, this is the first study showing an association between nuclear localization of Dvl and beta-catenin in IDCs and suggests the upregulation of Wnt/beta-catenin pathway components, beta-catenin, Dvl and cyclin D1 in IDCs of the breast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Cyclin D1 / metabolism*
  • Dishevelled Proteins
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Phosphoproteins / metabolism*
  • Signal Transduction
  • Up-Regulation
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Dishevelled Proteins
  • Phosphoproteins
  • Wnt Proteins
  • beta Catenin
  • Cyclin D1