Targeted expression of toxic genes directed by pituitary hormone promoters: a potential strategy for adenovirus-mediated gene therapy of pituitary tumors.

TLDR: It is suggested that adenoviral vectors carrying human pituitsary gland specific promoters may be useful for developing gene therapy strategies for the treatment of pituitary adenomas.

Abstract: Pituitary adenomas cause clinical manifestations because of mass effects and excess hormone production. This group of tumors represents a tractable target for gene therapy because they are rarely metastatic and because reductions in tumor size and function, in addition to those achieved after surgery, may be of clinical benefit. In this report we describe a strategy for targeting the expression of toxic genes to pituitary cells using adenoviral vectors. Pituitary hormone promoters (human GH or glycoprotein hormone α-subunit) were used to express either a marker gene [β-galactosidase (β-gal)] or a toxic gene[ herpes simplex virus thymidine kinase (TK)]. In GH-producing GH3 cells and in α-subunit-producing pituitary tumor cell lines, recombinant adenoviruses containing either the α-subunit promoter (AdαGal; AdαTK) or the GH promoter (AdGHGal; AdGHTK) were expressed at high levels. Using histological studies and assays forβ -gal activity, expression was shown to persist for at least 21 days, and it was relat...