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 dom ain of the estrogen or retinoic acid receptor, Murine fibrosarcoma L92 9 cells and human cervical carcinoma HeLa cells expressing the fusion proteins demonstrated apoptotic phenotypes in a tightly estrogen- or r etinoic acid-dependent manner in vitro. Moreover, the fusion protein-e xpressing L929 cells transplanted into nude mice were also killed thro ugh apoptosis after 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 im plies wide applications not only in developmental biology and neurobio logy but also in medicine, especially for cancer gene therapy.