TY - JOUR
T1 - Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia
AU - Yamada, Hiroyuki
AU - Iijima, Kazutoshi
AU - Tomita, Osamu
AU - Taguchi, Tomoko
AU - Miharu, Masashi
AU - Kobayashi, Kenichiro
AU - Okita, Hajime
AU - Saito, Masahiro
AU - Shimizu, Toshiaki
AU - Kiyokawa, Nobutaka
N1 - Funding Information:
Acknowledgments We thank Dr. Y. Matsuo for generous gifting of cell lines. We also thank H. Yagi for her excellent experimental assistance. This work was supported by a grant from Health and Labour Sciences Research Grants (the 3rd-term comprehensive 10-year strategy for cancer control H22-011), the Japan Health Sciences Foundation for Research on Publicly Essential Drugs and Medical Devices (KHA1002), the Grant of National Center for Child Health and Development (22A-5), Grant-in-Aid for Young Scientists (B) (23791211), and the Advanced research for medical products Mining Programme of the National Institute of Biomedical Innovation (NIBIO, 10-41, -42, -43, -44, -45).
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - B-cell precursor ALL
KW - Cell growth
KW - IGF-1
KW - IGFBP
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U2 - 10.1007/s12185-012-1234-3
DO - 10.1007/s12185-012-1234-3
M3 - Article
C2 - 23250859
AN - SCOPUS:84872923562
VL - 97
SP - 73
EP - 82
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 1
ER -