Abstract
We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the antitumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.
Original language | English |
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Pages (from-to) | 559-566 |
Number of pages | 8 |
Journal | Cancer Biology and Therapy |
Volume | 13 |
Issue number | 7 |
DOIs | |
Publication status | Published - May 2012 |
Keywords
- Akt
- Antitumor effect
- Apoptosis
- Bystander effect
- IGF-IR
- Truncated mutant
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research