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Hormone-induced Apoptosis by Fas-Nuclear Receptor Fusion Proteins: Novel Biological Tools for Controlling Apoptosis in Vivo¹

Departments of Pharmacology [H. T., H. O., K. F., M. Y., T. H., S. N., A. K.] and Pathology [M. F.], Kyoto University Faculty of Medicine, Kyoto 606-01, and Fukui Institute for Safety Research, Ono Pharmaceutical, Fukui 913 [H. O.], Japan

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 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 implies wide applications not only in developmental biology and neurobiology but also in medicine, especially for cancer gene therapy.

¹ This work was supported in part by research grants from the Ministry of Education, Science, Sports and Culture of Japan.

² To whom requests for reprints should be addressed. Phone: 81-75-753-4399; Fax: 81-75-753-4693.

Received 4/15/96. Accepted 7/17/96.

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