Antitumor effects of novel shorter truncated insulin-like growth factor I receptors

Yojiro Ojima, Atsushi Hongo, Yixuan Liu, Lisha Zhu, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Junichi Kodama, Yuji Hiramatsu

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1 Citation (Scopus)

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 languageEnglish
Pages (from-to)559-566
Number of pages8
JournalCancer Biology and Therapy
Volume13
Issue number7
DOIs
Publication statusPublished - May 2012

Keywords

  • Akt
  • Antitumor effect
  • Apoptosis
  • Bystander effect
  • IGF-IR
  • Truncated mutant

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Ojima, Y., Hongo, A., Liu, Y., Zhu, L., Kusumoto, T., Nakamura, K., Seki, N., Kodama, J., & Hiramatsu, Y. (2012). Antitumor effects of novel shorter truncated insulin-like growth factor I receptors. Cancer Biology and Therapy, 13(7), 559-566. https://doi.org/10.4161/cbt.19609