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.
Zeiger
M A
MA
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Md., USA.
Takiyama
Y
Y
Bishop
J O
JO
Ellison
A R
AR
Saji
M
M
Levine
M A
MA
D000256:Adenoviridae / Q000201:enzymology; D000257:Adenoviridae Infections / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D002277:Carcinoma / Q000556:secondary* / Q000628:therapy*; D016923:Cell Death; D002461:Cell Line, Transformed; D005240:Feasibility Studies; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D051381:Rats; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D013959:Thyroid Diseases / Q000473:pathology*; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000556:secondary* / Q000628:therapy*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir