Hormone-induced apoptosis by Fas-nuclear receptor fusion proteins: Novel biological tools for controlling apoptosis in vivo

We have created fusion proteins between Fas and the ligand-binding domain of the estrogen or retinoic acid receptor. Murine fibrosarcoma L929 cells and human cervical carcinoma HeLa cells expressing the fusion proteins demonstrated apoptotic phenotypes in a tightly estrogen- or retinoic acid- dependent manner in vitro. Moreover, the fusion protein-expressing L929 cells transplanted into nude mice were also killed through apoptosis alter injection of an estrogen agonist. This represents a novel system, 'cell targeting,' that can eliminate cells not only in vitro but also in vivo through the activation of a natural suicide machinery, i.e., apoptosis, by currently used hormones. This system implies wide applications not only in developmental biology and neurobiology but also in medicine, especially for cancer gene therapy.