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.
| Original language | English |
|---|---|
| Pages (from-to) | 73-82 |
| Number of pages | 10 |
| Journal | International Journal of Hematology |
| Volume | 97 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 Jan |
| Externally published | Yes |
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Keywords
- Apoptosis
- B-cell precursor ALL
- Cell growth
- IGF-1
- IGFBP
ASJC Scopus subject areas
- Hematology
Cite this
Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia. / Yamada, Hiroyuki; Iijima, Kazutoshi; Tomita, Osamu; Taguchi, Tomoko; Miharu, Masashi; Kobayashi, Kenichiro; Okita, Hajime; Saito, Masahiro; Shimizu, Toshiaki; Kiyokawa, Nobutaka.
In: International Journal of Hematology, Vol. 97, No. 1, 01.2013, p. 73-82.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84872923562&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872923562&partnerID=8YFLogxK
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 -