Recombinant Adenovirus that Mediate a Reversible Cell Cycle Arrest in Primary Oral Keratinocytes

Matthew A. Wettergreen and Guy R. Adami, Department of Oral Medicine and Diagnostic Sciences, Center for Molecular Biology of Oral Diseases, University of Illinois-Chicago, College of Dentistry, Chicago, IL, 60607

The ability to regulate the proliferation of normal cells in a reversible manner would be a useful adjunct to some clinical therapies including many types of cancer chemotherapy. While the application of recombinant growth factors and cytokines to target cells is a logical approach to regulate cell proliferation, high turnover rates of these peptide factors often make this approach impractical. The use of recombinant adenovirus to produce growth factors and cytokines in cells and tissues results in continuous localized expression of factors at functional levels over many days. We have adapted the tetracycline regulated expression system to allow regulated Transforming Growth Factor Beta (TGF-B) expression using recombinant adenovirus. We demonstrate that infection with recombinant TGF-B expression virus in primary human oral keratinocytes and a lung epithelial cell line is sufficient to allow a cell cycle arrest that is reversible upon tetracycline addition. This inhibition is efficient even after infection of a minority of cells in a population. These results highlight the possibility of using low-level infection with recombinant adenovirus to cause short-term blocks on cell proliferation.