Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins

Human papillomavirus (HPV) survives by reactivating DNA replication in post -mitotic cells. In the present study, we describe a mouse model of HPV-depe ndent disease, In these mice, DNA synthesis is activated in suprabasal kera tinocytes, leading to acanthosis, parakeratosis and enhanced desquamation, The full-length E6/E7 transcript and two alternately spliced products are p roduced and in most lines the predominant product is E6*, In the present st udy, we examine the effects of E6/E7 on cell cycle regulatory protein expre ssion. E6/E7 expression in mouse epidermis is correlated with increased lev els of the p53, p21, p27, cdk2, cdk4, cdk6, cyclin D1 and cyclin E regulato ry proteins. Hyperproliferation is also observed in the buccal mucosa and t he tongue epithelia of E6/E7 mice, and p53 levels are markedly increased in these epithelia, These results suggest that the major changes in cell cycl e regulatory protein expression are in response to the presence of E7 and t hat E6 has a lesser impact.