γ-Secretase Inhibitors Induce Erythroid Differentiation in Erythroid Leukemia Cell Lines

被引：0

作者：

Okuhashi, Yuki ^{[1
]}

Itoh, Mat ^{[1
]}

Arai, Ayako ^{[2
]}

Nara, Nobuo ^{[1
]}

Tohda, Shuji ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Dept Lab Med, Bunkyo Ku, Tokyo 1138519, Japan

[2] Tokyo Med & Dent Univ, Dept Hematol, Bunkyo Ku, Tokyo 1138519, Japan

来源：

ANTICANCER RESEARCH | 2010年 / 30卷 / 10期

基金：

日本学术振兴会;

关键词：

Notch; gamma-secretase inhibitor; erythroid leukemia; differentiation; GROWTH; JAGGED1; NOTCH1; DEATH;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Notch signaling regulates the fate of hematopoietic stem cells and leukemia cells. However, the role of Notch in erythroid differentiation remains unclear. Materials and Methods: We examined the effects of three gamma-secretase inhibitors (GSI-IX, GSI-XII and GSI-XXI) that inhibit Notch signaling on the in vitro growth and differentiation of HEL and AA erythroid leukemia cell lines. Results: GSI treatment induced morphologic erythroid differentiation and promoted hemoglobin production. GSI treatment suppressed short-term growth and colony formation, while treatment with GSI-XXI promoted the growth of AA cells. The degree of differentiation induced by each GSI roughly correlated with the reduction in HESI mRNA expression. Conclusion: GSIs have potential uses in differentiation induction therapy for erythroid leukemia in the future. Before clinical use, in vitro sensitivity tests should be performed because the effects of GSIs are diverse depending upon the combination of leukemia cells and GSIs.

引用

页码：4071 / 4074

页数：4

共 13 条

[1] mNotch1 signaling and erythropoietin cooperate in erythroid differentiation of multipotent progenitor cells and upregulate β-globin [J].

Henning, Konstanze ;

Schroeder, Timm ;

Schwanbeck, Ralf ;

Rieber, Nikolaus ;

Bresnick, Emery H. ;

Just, Ursula .

EXPERIMENTAL HEMATOLOGY, 2007, 35 (09) :1321-1332

[2] Notch signals inhibit the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through the induction of HES1 [J].

Ishiko, E ;

Matsumura, I ;

Ezoe, S ;

Gale, K ;

Ishiko, J ;

Satoh, Y ;

Tanaka, H ;

Shibayama, H ;

Mizuki, M ;

Era, T ;

Enver, T ;

Kanakura, Y .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (06) :4929-4939

[3] Notch-1 regulates cell death independently of differentiation in murine erythroleukemia cells through multiple apoptosis and cell cycle pathways [J].

Jang, MS ;

Miao, HX ;

Carlesso, N ;

Shelly, L ;

Zlobin, A ;

Darack, N ;

Qin, JZ ;

Nickoloff, BJ ;

Miele, L .

JOURNAL OF CELLULAR PHYSIOLOGY, 2004, 199 (03) :418-433

[4]

Kogoshi H, 2007, ONCOL REP, V18, P77

[5] γ-secretase:: proteasome of the membrane? [J].

Kopan, R ;

Ilagan, MXG .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (06) :499-504

[6] Recent insights into the role of Notch signaling in tumorigenesis [J].

Leong, KG ;

Karsan, A .

BLOOD, 2006, 107 (06) :2223-2233

[7] Diaminofluorene stain detects erythroid differentiation in immature haemopoietic cells treated with EPO, IL-3, SCF, TGFβ1 , MIP-1α and IFNγ [J].

McGuckin, CP ;

Forraz, N ;

Liu, WM .

EUROPEAN JOURNAL OF HAEMATOLOGY, 2003, 70 (02) :106-114

[8]

Okuhashi Y, 2010, ANTICANCER RES, V30, P495

[9] The notch pathway positively regulates programmed cell death during erythroid differentiation [J].

Robert-Moreno, A. ;

Espinosa, L. ;

Sanchez, M. J. ;

de la Pompa, J. L. ;

Bigas, A. .

LEUKEMIA, 2007, 21 (07) :1496-1503

[10] Notch signaling in hematopoietic stem cells [J].

Suzuki, T ;

Chiba, S .

INTERNATIONAL JOURNAL OF HEMATOLOGY, 2005, 82 (04) :285-294

← 1 2 →