Growth inhibition of human melanoma cells in nude mice by antisense strategies to the type 1 insulin-like growth factor receptor.
The growth of human melanoma cells FO-1 in nude mice is strongly inhibited or even abrogated when the cells are stably transfected with a plasmid expressing an antisense RNA to the insulin-like growth factor 1 receptor (IGF-1R) RNA, which causes a marked reduction in the number of IGF-1 receptors. When a tumor arises after a long delay in nude mice, it can be shown that the tumor cells have lost the expression plasmid and that the number of IGF-1 receptors has returned to wild-type levels. The antisense effect is even more remarkable, since the growth of FO-1 melanoma cells in monolayers is not affected by the expression of the antisense RNA. Inhibition of tumorigenesis was also evident when FO-1 melanoma cells were treated with antisense oligodeoxynucleotides to the IGF-1R RNA prior to injection into nude mice. These results confirm in human cells that the IGF-1R plays a dominant role in transformation and tumorigenesis and that its effect on tumorigenesis is more profound than its effect on mitogenesis.
Resnicoff
M
M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Coppola
D
D
Sell
C
C
Rubin
R
R
Ferrone
S
S
Baserga
R
R
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids / Q000008:administration & dosage / Q000032:analysis; D016372:RNA, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors*; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection
D016372:RNA, Antisense; D012334:RNA, Neoplasm; D017526:Receptor, IGF Type 1