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 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.
Takebayashi
H
H
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Oida
H
H
Fujisawa
K
K
Yamaguchi
M
M
Hikida
T
T
Fukumoto
M
M
Narumiya
S
S
Kakizuka
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002522:Chlorocebus aethiops; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004964:Estriol / Q000494:pharmacology; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016324:Sequence Tagged Sites; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology*
D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D013629:Tamoxifen; D004958:Estradiol; D014212:Tretinoin; D004964:Estriol