Abstract
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.
Footnotes
-
↵1 Supported by Grants CA 53484 and GM 33694 from the NIH.
-
↵2 To whom requests for reprints should be addressed, at Kimmel Cancer Center. Thomas Jefferson University, 624 Bluemle Life Sciences Building, 233 South 10th Street, Philadelphia, PA 19107. Phone: (215) 503-4507; Fax: (215) 923-0249; E-mail: Basergal@jeflin.tju.edu.
- Received March 14, 1996.
- Accepted June 28, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 17
