Studies on in vivo gene transfer in pituitary tumors using herpes-derived and adenoviral vectors

Abstract

Suicide gene therapy has met limited success for the treatment of rat pituitary tumors. In order to determine the cause of primary pituitary tumor resistance to suicide gene therapy, we studied the transgene expression of an adenoviral (Ad.RSV.βgal.nls) and a herpes simplex virus-derived ( tsK/β-gal) vector, both harboring the β-galactosidase reporter gene in rat prolactinomas. Rats carrying experimental prolactinomas received bilateral 1 μl intrapituitary injections of either saline (saline group), 5 × 10 5 plaque-forming units (pfu) tsK/β-gal (HSV Group) or 5 × 10 5 pfu Ad.RSV.βgal.nls (RAd Group). Two or seven days later the tumors were examined. Macroscopic inspection of glands injected with either vector showed that the tissue expressing β-gal was concentrated at the ventral area around the site reached by the tip of the needle. Almost no transgene expression was observed in other sites. Cellularity and lactotrophic cell density was not affected by saline or virus injection. In the injected areas, apoptotic levels were ( x ¯ ± S.E.M.): 9.3 ± 0.5, 22.1 ± 1.1 and 31.7 ± 1.4%, for the saline, RAd and HSV groups, respectively. Serum prolactin and growth hormone levels were not affected by virus injection. We conclude that the low diffusibility of viral suspensions in the pituitary tissue may constitute a significant obstacle for achieving full remission of in situ pituitary tumors in rats.