Study of the effects of epidermal growth factor on genomic instability and malignant phenotype of oral squamous cell carcinoma cells

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Growth factors can enhance the malignant potential of tumor cells. To study the effects of epidermal growth factor(EGF) on invasion and metastasis of human oral squamous cell carcinoma, we examined the intercellular signal transduction of EGP-induced motility using an EGF sensitive S-1 clone cell line, obtained from Ca9-22 cell line. EGF -treatde S-1 cells were affected some blocking chemicals, and moduration of random motility was examined by phagokinetic track assay.When the cells were treated with erbstatin analog; to inhibit tyrosine phosphorylation, or psi-tectorigenin to inhibit phosphatidyl-inositol turnover the motility enhanced by EGF was completely inhibited. When phorbol 12-myristate 13-acetate(PMA) was used, to stimulate protein kinase C(PKC), motility in the absence of EGF was enhanced similar to that of EGF stimulation. Calphostin C, an inhibitor of PKC activation, completely eliminated the EGF-induced enhancement of motility. Examination of the intercellularlocalization of PKC with a confocal laser microscope showed enhanced expression of PKC and transduction of PKC to membrane area after EGF stimulation. These results suggest that activation of phospholipase C-v (PLC) caused by auto-phosphorylation of EGF receptor might play an important role in the signal transduction of EGF induced cell motility.To examine the relationship between growth factor and tumor progression, we pleviously established a weakly malignant cell line, ER-1, from rat mammary carcinoma cell line in female SHR rat. We found that a 24-hour exposure of ER-1 celisto EGF induced malignant properties that were reversible but that, after a 1-month exposure, these changes were irreversible. In DNA fingerprinting as abnormal bands were observed in ER-I cells after long-term EGE stimulation. These results suggest that long-term EF stimulation can affect the genomic instability of ER-I cells.