title: Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia.
abstract: Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Iijima
authors.forename: Osamu
authors.initials: O
authors.lastname: Tomita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Taguchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Miharu
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Saito
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1