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 anti-tumor 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.
authors.affiliation: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Ojima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hongo
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhu
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kusumoto
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Noriko
authors.initials: N
authors.lastname: Seki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiramatsu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D024201:Bystander Effect / Q000187:drug effects; D016466:CHO Cells; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D017526:Receptor, IGF Type 1