Establishment and characterization of a tracheal epithelial cell line RTEC11 from transgenic rats harboring temperature-sensitive simian virus 40 large T-antigen

Transgenic animals, mice and rats, harboring temperature-sensitive simian virus 40 large T-antigen have been found to be very useful for establishing immortalized cell lines from tissues that have been proved difficult to culture in vitro. Here, we succeeded in establishing a conditionally immortalized tracheal epithelial cell line RTEC11 from adult transgenic rats harboring the oncogene. Morphological and functional investigations demonstrated that the RTEC11 cells were polarized epithelial cells maintaining a regulated permeability barrier function. Although the large T-antigen was expressed in the nuclei and the cells grew continuously at a permissive temperature of 33 ̊C, the down regulation of large T-antigen at a nonpermissive temperature of 39 ̊C was associated with cell growth arrest and cellular differentiation. In addition, global gene expression and computational network analyses indicated that a significant genetic network including CDKN1A was associated with cellular differentiation induced by inactivation of the large T-antigen. The tracheal epithelial cell line RTEC11 with unique characteristics should be useful as an in vitro model of the tracheal epithelium for physiological, pharmacological and toxicological investigations. Moreover, experiments using an immortal cell line may offer an alternative to experiments using living animals.