Inverse relationship between E-cadherin and p27Kip1 expression in renal cell carcinoma.
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.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. toshiro.migita@jfcr.or.jp
Toshiro
T
Migita
Yoshinao
Y
Oda
Katsuaki
K
Masuda
Akira
A
Hirata
Michihiko
M
Kuwano
Seiji
S
Naito
Masazumi
M
Tsuneyoshi
D015820:Cadherins / Q000032:analysis / Q000502:physiology*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D007680:Kidney Neoplasms / Q000473:pathology*
C436291:CDKN1B protein, human; D015820:Cadherins; D019927:Cyclin E; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors