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○○○○○m-induced diffrentiation in cultures of human oral keratinocytes provides an excellent in vitro model to study difffrentiation. To understand the genetic events that underlie keratinocyte differentiation, we cultured the human papillomavirus type 16 (HPV-16)-immortalized human oral teratinorytes in medium containing 0.15, 0.3, 0.6, or 1.2 mM of calcium fur 3 days and determined the degree of cell differentiation and expression of c-fos, c-myc, c-Ha-ras, and epidermal growth factor receptor (EGFR) genes from the cells. Calcium, in a concentration-dependent manner, increased the cell differentiation. Calcium had no effect on the levels of c-mye and c-fos expression. The transcription of c-Ha-ras and EGFR messages, however, was, increased by high concentration of calcium (1.2 mM), suggesting transcriptional regulation of these ge○○○○during differentiation. These results indicate that expression of c-myc and c-fos does not have an obhgate role in the keratinocyte differentiation precess, but enhanced levels of c-Ha-ras and EGFR gene messages may be, in part, responsible for the cell differentiation. These findings expand our knowledge of the differentiation process in human oral keratinocytes.
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