An adenoviral system for tetracycline-regulated TGF-beta expression mediates a reversible cell cycle arrest.
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 and surgery for periodontal regeneration. While the application of recombinant growth factors and cytokines to target cells is a logical approach to regulate cell proliferation, the high turnover rates of these peptide factors often make this approach impractical. Recombinant 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 regulated transforming growth factor (TGF)-beta1 expression using recombinant adenovirus. 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 upon tetracycline addition. This inhibition is efficient even after the 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.
Wettergreen
M A
MA
Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois at Chicago, USA.
Hunniford
J W
JW
Crawford
J M
JM
Adami
G R
GR
D000256:Adenoviridae / Q000235:genetics*; D017498:Adenovirus E1 Proteins / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology*; D015534:Trans-Activators / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019076:Transgenes / Q000502:physiology
D017498:Adenovirus E1 Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D013752:Tetracycline