Cell transformation by papovaviruses requires the expression of several early viral gene products. Our laboratory is currently investigating the mechanism by which papillomaviruses (human and bovine) and polyomavirus perturb cell growth control and participate in tumorigenesis. The main research focus will be on human papillomaviruses (HPV). Although the role of HPV in benign human tumors (warts) is well established, it is only recently that an association between HPV and cervical cancer has been defined. More than 31 types of HPV exist (by DNA hybridization). Only a few of these HPVs are associated with cervical cancer, however. For example, type 16 appears to be found in various stages of cervical dysplasia (or """"""""flat warts"""""""") as well as in carcinoma-in-situ and invasive carcinoma. Type 18 HVP is found only in invasive cervical carcinoma. The biological role of these viral genomes in tumor cells is unknown, but the ability of related bovine papillomaviruses (BPV) to transform cells in vitro suggests that HPV may have a role in either initiating or maintaining the transformed state. We will attempt to determine whether human cervical carcinoma lines contain dominant transforming genes using transfection techniques and will also attempt to transform cells in vitro with HPV DNA. Selected, formal studies with BPV will be performed for comparison of HPV and BPV transforming properties. Related to our attempts to transform cells with HPV is an effort to transform epithelial cells in vitro. Our laboratory has an interest in defining the progressive stages of carcinogenesis and, as part of this study, to establish an in vitro system for the transformation of epithelial cells. We have decided to focus on human and murine epidermal cells since much is known about the murine model for the induction of squamous cell carcinoma and since thee cells can be propagated in vitro. Culture conditions for human epidermal cells are also well established. Our initial attempt will include transfecting murine epidermal cells with BPV and polyoma DNA and human epidermal cells with HPV-16 and HPV-18 DNA.
