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Growth Inhibition of Human Melanoma Cells in Nude Mice by Antisense Strategies to the Type 1 Insulin-like Growth Factor Receptor¹

Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [M. R., D. C., C. S., R. R., R. B.] Department of Microbiology and Immunology, New York Medical College, Valhalla, New York [S. F.]

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.

¹ This work was supported by NIH Grants CA 53484 (R. B.), CA 56309 (R. B.), CA 37959 (S. F.), and CA 51814 (S. F.).

² To whom requests for reprints should be addressed, at Thomas Jefferson University, Jefferson Cancer Institute, Bluemle Life Sciences Building, 233 South 10th Street, Philadelphia, PA 19107-5541.

Received 8/ 2/94. Accepted 8/15/94.

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