A soluble insulin-like growth factor I receptor that induces apoptosis of tumor cells in vivo and inhibits tumorigenesis
D'Ambrosio, C.; Ferber, A.; Resnicoff, M.; Baserga, R.
Cancer Research 56(17): 4013-4020
1996
ISSN/ISBN: 0008-5472 PMID: 8752172 Document Number: 456366
By a frame-shift mutation, we have engineered a human IGF-I receptor (IGF-IR) cDNA that produces a receptor 486 amino acids long (plus the 30 amino acids of the signal peptide). This receptor, which we have designated as 486/STOP, is partially secreted into the medium of cells in culture and markedly inhibits the autophosphorylation of the endogenous IGF-IRs as well as the activation of the signaling pathway. The 486/STOP receptor acts as a strong dominant negative for several growth functions: (a) it inhibits the growth of cells in monolayers; (b) it inhibits the growth of transformed cells in soft agar; (c) it induces extensive apoptosis in vivo; and (d) it inhibits tumorigenesis in syngeneic rats. This is the first demonstration that a dominant negative of the IGF-IR can induce massive apoptosis of tumor cells in vivo.