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

doi:10.4161/cbt.19609

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

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	559-566
Number of pages	8
Journal	Cancer Biology and Therapy
Volume	13
Issue number	7
DOIs	https://doi.org/10.4161/cbt.19609
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

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title = "Antitumor effects of novel shorter truncated insulin-like growth factor I receptors",

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.",

keywords = "Akt, Antitumor effect, Apoptosis, Bystander effect, IGF-IR, Truncated mutant",

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

note = "Funding Information: {\textcopyright} 2012 Landes Bioscience. Medical University) for a fruitful discussion. This study was supported in part by Grant-in- aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and",

year = "2012",

month = may,

doi = "10.4161/cbt.19609",

language = "English",

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T1 - Antitumor effects of novel shorter truncated insulin-like growth factor I receptors

AU - Ojima, Yojiro

AU - Hongo, Atsushi

AU - Liu, Yixuan

AU - Zhu, Lisha

AU - Kusumoto, Tomoyuki

AU - Nakamura, Keiichiro

AU - Seki, Noriko

AU - Kodama, Junichi

AU - Hiramatsu, Yuji

N1 - Funding Information: © 2012 Landes Bioscience. Medical University) for a fruitful discussion. This study was supported in part by Grant-in- aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and

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