Inverse relationship between E-cadherin and p27Kip1 expression in renal cell carcinoma

Int J Oncol. 2008 Jul;33(1):41-7.


The cell-cell adhesion system plays a pivotal role in the maintenance of tissue structure and cell-cell communication. E-cadherin is a major adhesion protein of the epithelial cells, and E-cadherin expression may be involved in the regulation of cell proliferation or differentiation. To address the relationship between cell-cell adhesion and cell proliferation, we focused on the alteration of p27Kip1 (p27), a cyclin-dependent kinase inhibitor, by E-cadherin-mediated adhesion. In an immunohistochemical study of 76 cases of renal cell carcinoma (RCC), the p27-labeling index (LI) was 67% in E-cadherin-reduced RCC, but only 28% in E-cadherin-preserved RCC. E-cadherin-expressing cells rarely expressed p27 in various cancers including those of the breast, colon, liver and prostate. In a subconfluent monolayer culture, the E-cadherin levels were increased steadily in the E-cadherin positive RCC cell line ACHN, whereas the p27 levels were decreased. Subsequent exposure of ACHN cells to the E-cadherin-specific function-blocking antibody reduced the growth associated with the increase in p27 and the decrease in phosphorylated epidermal growth factor receptor (EGFR). In the E-cadherin negative RCC cell line Caki-1, these effects were not observed. These results suggest that E-cadherin-mediated adhesion may be involved in the contact stimulation for cell proliferation in part through the downregulation of p27 and the activation of EGFR in human cancers.

MeSH terms

  • Cadherins / analysis
  • Cadherins / physiology*
  • Carcinoma, Renal Cell / pathology*
  • Cell Communication
  • Cell Line, Tumor
  • Cyclin E / analysis
  • Cyclin-Dependent Kinase Inhibitor p27
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Kidney Neoplasms / pathology*


  • CDKN1B protein, human
  • Cadherins
  • Cyclin E
  • Intracellular Signaling Peptides and Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • ErbB Receptors