Conditional gene expression in human intracranial xenograft tumors

In an initial effort to determine the effect of expressing potentially therapeutic gene products on the growth properties of glioma tumor xenografts, we describe the development of cell lines that can conditionally express beta-galactosidase (beta-gal). To achieve this, we generated stable cell lines that express the modified tetracycline repressor molecule (rtTA) and the beta-gal gene under control of tetracycline-responsive cis-elements. The resulting cell lines express functional beta-gal following treatment with the tetracycline analog doxycyclin (Dox). These cells were then used to form intracranial tumors after injection into the brain using an implantable guide-screw system. The xenografts were found to express beta-gal when the animals were fed drinking water containing Dox. From these studies, we conclude that the expression of a target gene in a human xenograft growing in the brain of a living mouse can be conditionally regulated.