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.
Migita
Toshiro
T
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. toshiro.migita@jfcr.or.jp
Oda
Yoshinao
Y
Masuda
Katsuaki
K
Hirata
Akira
A
Kuwano
Michihiko
M
Naito
Seiji
S
Tsuneyoshi
Masazumi
M
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