Abstract
The mechanism of carcinogenesis induced by 4-nitroquinoline 1-oxide remains poorly understood.
We studied cell kinetics (BrdU, cyclin D 1) and immunohistochemically examined the relation to the cell cycle and morphogenesis (P-cadherin) to determine the mechanism of carcinogenesis. P-cadherin is a cell adhesion molecular essential for morphogenesis. It also has an important role in cell proliferation. However, the role of P-cadherin in carcinogenesis remains unclear.
During the epithelial dysplasia stage of carcinogenesis, BrdU and cyclin D 1 were overexpressed significantly as compared with normal epithelial tissue (p=0.0005). The localization of cyclin D 1 and Pcadherin extended from the basal cells to the spinous cell layer. This localization of cyclin D 1 indicated that cells in the spinous cell layer were in the G 1 phase of their cell cycle. P-cadherin simultaneously appeared on their cell membrane.
Our results suggest that overexpression of P-cadherin is closely related to the G 1 phase of the cell cycle and that carcinogenesis is induced by an uncontrolled cell cycle with overexpression of P-cadherin.