Malignant transformation of primary human oral squamous epithelial cells using a defined set of genetic alterations

Normal keratinocytes display a restricted replicative life span. Therefore, senescence has been thought to form a barrier against carcinogenesis and the acquisition of cellular immortalization is considered an essential step in the malignant transformation of normal cells. Several groups have demonstrated that the serial introduction of the SV40 early region, H-rasV12 and h-TERT sufficed to transform several types of human cells in vitro, although this combination is rarely seen in human cancer. In contrast, cyclin D1 overexpression, inactivation of p53, EGFR overexpression as well as c-myc overexpression are co…