An adenoviral system for tetracycline-regulated TGF-beta expression mediates a reversible cell cycle arrest

The ability to regulate the proliferation or normal cells in a reversible m anner would be a useful adjunct to some clinical therapies. including many types of cancer chemotherapy and surgery for periodontal regeneration. Whil e the application of recombinant growth factors and cytokines to target cel ls is a logical approach to regulate cell proliferation, the high turnover rates of these peptide factors often make this approach impractical. Recomb inant adenoviral vectors can be used to direct the expression of transgene products Such as growth factors in many cell types in vitro and in vivo. We have adapted the tetracycline-regulated expression system to allow regulat ed transforming growth factor (TGF)-beta1 expression using recombinant aden ovirus. We demonstrate that infection with a recombinant TGF-beta -encoding virus system in primary human oral keratinocytes and in a lung epithelial cell line is sufficient to allow a cell cycle arrest that is reversible upo n tetracycline addition. This inhibition is efficient even after the infect ion of a minority of cells in a Population. These results highlight the pos sibility of using low level infection with recombinant adenovirus to cause short-term blocks on cell proliferation.