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 inhib ited or even abrogated when the cells are stably transfected with a pl asmid expressing an antisense RNA to the insulin-like growth factor 1 receptor (IGF-1R) RNA, which causes a marked reduction in the number o f 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 plasmi d and that the number of IGF-1 receptors has returned to wild-type lev els. The antisense effect is even more remarkable, since the growth of FO-1 melanoma cells in monolayers is not affected by the expression o f 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 co nfirm in human cells that the IGF-1R plays a dominant role in transfor mation and tumorigenesis and that its effect on tumorigenesis is more profound than its effect on mitogenesis.