Transgenic animal models of human papillomavirus-dependent disease (review)

Human papillomaviruses (HPVs) are DNA tumor viruses that induce hyperprolif erative lesions in cutaneous and mucosal epithelia. A wide variety of studi es implicate the viral E6 and E7 oncoproteins as cell immortalizing agents, and show that these proteins work, respectively, by interfering with the f unction of the p53 and pRb tumor suppressor genes. Most of these studies ha ve been performed using cell culture models. However, recently, a variety o f in vivo mouse model systems have been developed for the study of HPV-depe ndent disease. These models use tissue-specific promoters to deliver HPV on coprotein expression to specific body sites. Using this strategy, mouse mod els have been designed for the study of cancer progression in epithelia, an d additional models have been designed to use E6 and E7, respectively, to p robe the role of p53 and pRb on tissue differentiation and function. In the present report, we summarize the literature describing these systems, and highlight some of the important findings derived from these studies.