ADENOVIRAL INFECTION OF THYROID-CELLS - A RATIONALE FOR GENE-THERAPY FOR METASTATIC THYROID-CARCINOMA

Background. Patients with thyroid carcinoma experience excellent long- term survival; however, up to 16% will die of their disease. We have t ransformed a rat thyroid follicular cell line (FRTL-5) with a gene (TG CT) that mimics a Known mutation associated with thyroid neoplasms. Th ese cells form subcutaneous tumors that metastasize to lung in nude mi ce. Methods, In anticipation of developing gene therapy against this t hyroid carcinoma model, we (1) tested whether adenovirus containing th e beta-galactosidase gene could infect FRTL-5 cells and. neonatal rat thyroid and (2) evaluated the ability to kill FRTL-5 cells by transfec ting them with a transgene in which the thyroglobulin promoter (TG) di rected the expression of herpes simplex virus type I thymidine Kinase (HSV1TK) and treating TG-HSV1TK-transfected cells with 5 mu g/ml ganci clovir. Results, Nearly 100% of the TG-HSV1TK but only 5% of control c ells were killed by addition of ganciclovir. Histochemical staining fo r beta-galactosidase activity demonstrated infection of FRTL-5 cells a nd neonatal rat thyroid tissue by adenovirus beta-galactosidase. Concl usions, These data demonstrate the feasibility of using adenovirus as vector to infect thyroid cells in vivo and provide a rationale for dev elopment of gene therapy for treatment of thyroid cancer.