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 transformed a rat thyroid follicular cell line (FRTL-5) with a gene (TGCT) that mimics a known mutation associated with thyroid neoplasms. These cells form subcutaneous tumors that metastasize to lung in nude mice.

Methods: In anticipation of developing gene therapy against this thyroid carcinoma model, we (1) tested whether adenovirus containing the beta-galactosidase gene could infect FRTL-5 cells and neonatal rat thyroid and (2) evaluated the ability to kill FRTL-5 cells by transfecting them with a transgene in which the thyroglobulin promoter (TG) directed the expression of herpes simplex virus type I thymidine kinase (HSV1TK) and treating TG-HSV1TK-transfected cells with 5 micrograms/ml ganciclovir.

Results: Nearly 100% of the TG-HSV1TK but only 5% of control cells were killed by addition of ganciclovir. Histochemical staining for beta-galactosidase activity demonstrated infection of FRTL-5 cells and neonatal rat thyroid tissue by adenovirus beta-galactosidase.

Conclusions: These data demonstrate the feasibility of using adenovirus as vector to infect thyroid cells in vivo and provide a rationale for development of gene therapy for treatment of thyroid cancer.