ANALYSIS OF THE SIGNAL TRANSDUCTION OF CELL MOTILITY INDUCED BY EGF STIMULATION IN HUMAN ORAL CANCER CELLS

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In order to clear the effects of Epidermal Growth Factor (EGF) on the invasion abilities of human oral squamous cell carcinoma, five cell lines were studied. EGF enhanced the random motility of all cell lines in a dose-dependent fashion and exposure to EGF let to an increased production of urokinase type plasminogen activator and matrix metalloproteniase-9 by the same cells. These results strongly suggest the EGF may promote the invasion and metastasis of human oral squamous cell carcinomas. In this project, to reveal the signal pathway, we established s-1 clone cells, which was most sensitive clone against the EGF stimulation and also we established i-1 clone cells, which was most insensitive clone. Further studies were done using s-1 clone cells. When EGF bind to the EGF receptor, tyrosine phosphorelation is firstly occurred and subsequently PKC is activated through the activation of PLCr arising from erbB homodimer and/or activation of PI3-kinase arising from erbB3 heterodimer. Furthermore, erbB homodimer activates the nPKCd through the activation of PLC and also erbB/erbB-3 heterodimer activates aPKCe through the activation of PI3K. These results suggest that inhibition of aPKCe or nPKCd can reduce the invasion and metastasis of human oral cancer cells and that the useful model in the investigations of molecular target medicines is possibly established.